The spontaneously hypertensive rat model with reduced NO synthesis (SHRLN) shares features with aging and hypertension in humans, among other a severe aortic stiffening. The present
The stiffening of large central arteries occurs naturally with aging. The reduction of aortic compliance leads to downstream damage to organs which receive high flow with low impedance such as the brain [
Recently, we investigated the role of an increased salt diet in hypertensive rat on aortic stiffness [
In the present study we aimed to evaluate thoracic and abdominal arterial compliance and composition in another experimental model of hypertensive aortic stiffness. For that purpose, we administered L-NAME in spontaneously hypertensive rats (SHR) over 5 weeks and studied aortic compliance using echotracking evaluation of pressure-independent stiffening [
This study was conducted in accordance with European Community Guidelines for the use of experimental animals and was approved by the ethical committee on Animal Experiments of the Servier Research Institute. All animals were provided by CERJ (France). Three groups were compared: Wistar Kyoto (WKY) rats (n=6), SHR (n=6), and SHR given N-nitro-L-arginine methyl ester (L-NAME, Sigma) at 2 mg/kg in drinking water for 5 weeks, from 15 to 20 weeks of age (SHRLN) (n=8). Water consumption and body weight were measured every 3 days and L-NAME concentration was adjusted to maintain 2 mg/kg/day. The animals were housed 2 per cage in a temperature controlled room (20-21°C) with a 12/12 hour light/dark cycle.
Rats were anaesthetized with an intraperitoneal injection of sodium pentobarbital (50mg/kg i.p. for induction, maintained with 5mg/kg/h i.v. to obtain a stable level of anaesthesia). The jugular vein was cannulated for constant administration of anesthetic and the penile vein was cannulated for administration of other drugs. The trachea was cannulated and ventilation was maintained with a pressure controlled respirator (Hallowell EMC, TEM) at a frequency of 60-70 cycles per minute and a pressure of 9-12 cmH2O. Body temperature was maintained at 37°C with a homeothermic blanket (Harvard) connected to a rectal probe.
A microtip pressure catheter (Millar 1.2F) was inserted into the aorta via the right femoral artery. The blood pressure signal was visualized and analyzed with Biopac 4.2 Acknowledge acquisition and analysis system (CEROM). The aortic diameter was simultaneously measured as previously described [
Thoracic measurements were made at the lowest part of the TA, above renal artery bifurcation and below diaphragm and abdominal aorta measurements were made at the lowest abdominal site.
The catheter was inserted first into the TA via the right femoral artery and measurements were made in the TA at baseline blood pressure. Then the catheter was withdrawn and placed in the AA just above the iliac bifurcation. The ultrasound was also moved to obtain an image of the catheter within the AA. For the SHR group, after the baseline recordings, a second series of measurements were taken within the AA when blood pressure was reduced using an injection of clonidine (3
The parameters automatically calculated to determine the dynamic properties of the aortic wall were as follows: mean diameter (
Additionally we analyzed as previously described [
Two more groups of SHR, one with L-NAME in drinking water as described above (n=9) and one without (n=8), were implanted with a standard telemetric device (TA11PA-C40, Data Sciences International, the Netherlands) with a pressure transducer under short-term anesthesia with isoflurane. Blood pressure signals were continuously recorded by data analysis software (Dataquest ART®, DSI). Systolic (SBP), diastolic (DBP), mean blood pressure (MBP), pulse pressure (PP), and heart rate (HR) were automatically detected beat to beat with analysis software ECG auto® (v3.0.0.18, EMKA, France) and averaged every minute.
Data were analyzed 1 day before L-NAME treatment and then at days 7, 14, 21, and 28 of treatment and similarly for the control SHR group. Reported values of SBP, DBP, MBP, and PP, represented the mean of individual measurements over the 24 h recording period. Short-term variability of HR, SBP, DBP, and PP was calculated over 1-minute periods over 24h Average Real Variability (ARV), an index used in clinical studies, considered as the most potent index for short-term BP variability, evaluates the variability between consecutive and validated readings [
Urines were collected during 24 hours 3 days before the end of the protocol; proteinuria and the urinary ratio protein/creatinine were measured (ABX PENTRA C400).
At the end of the experiments the rats were euthanized via a lethal dose of sodium pentobarbital i.v. Rat nasorectal length was measured. The left ventricle and left kidney were weighed. Left ventricle and left kidney weight were normalized to their ratio to nasorectal length (mg/cm). Thoracic and abdominal aortas were cleaned and stored in 4 % formaldehyde.
Arterial structure was determined and quantified in 4% formaldehyde-fixed thoracic and abdominal aortas extracted from the rats used for hemodynamic measurements. For that purpose, a piece of about 5 mm long, corresponding to the same site used for ultrasound measurements for both TA and AA, was cut and embedded in paraffin. The tissue was then extracted from individual paraffin blocks and inserted into a preformed paraffin recipient block (Tissue-Tek Quick-Ray System, Sakura Finetek France). The finished block was then cut into 4
Media cross-sectional areas (MCSA) and scleroproteins quantifications were performed by morphological analysis after a Sirius red and a three-color staining protocol (Masson’s trichrome) as previously described [
For immunohistochemical analyses of cell-matrix interactions, a fibronectin polyclonal antibody (ab2040, Millipore) was used. Integrins accumulation was quantified with
Heat-mediated antigen retrieval was performed in EDTA buffer pH 9 in a water bath for 30 min. Immunostaining was performed on a Dako autostainer using a peroxidase-labeled polymer-based detection system (Envision plus, Dako) and diaminobenzidine as a chromogen. No specific staining was observed when primary antibody was omitted from the protocol (negative control). The distribution and quantification of staining were determined by computer-directed color analysis performed with the noncommercial image processing software Mesurin® [
All data were expressed as the mean ± the standard error of the mean (SEM). Then each hemodynamic parameter was analyzed with a one way ANOVA of raw data followed by a Tukey post-hoc comparison first at basal blood pressure and again at matched blood pressures across the three groups. Time effect was analyzed by a one WAY ANOVA followed by a Dunnett’s test. Paired Student t test was performed to compare thoracic and abdominal values, as well as the effect of clonidine in hypertensive rats.
For immunochemistry analysis, two-way ANNOVA on groups and sites was performed followed by a Tukey’s multiple comparison test.
Differences were considered significant at values of P<0.05.
A slight reduction of body weight was observed in the SHRLN group. No groups presented with renal hypertrophy as determined by no change in animal-length normalized kidney weights. This was observed despite a reduction in kidney function in the SHRLN as determined by increased total proteinuria/24h and by the increased ratio urinary protein/creatinine (Table
Parameters for the model characterization.
WKY | SHR | SHRLN | ||
---|---|---|---|---|
Body weight | g | 432 ± 3 | 398 ± 12 | 373 ± 15 |
Left ventricle weight | mg/cm | 32.8 ± 0.4 | 45.2 ± 1.3 | 50.4 ± 1.0 |
Kidney weight | mg/cm | 53.8 ± 8 | 54.1 ± 1.6 | 56.7 ± 1.7 |
24h proteinuria | mg/24h | 0.98 ± 0.09 | 9.50 ± 1.12 | 47.3 ± 12.5 |
Protein/creatinine | 0.65 ± 0.01 | 0.69 ± 0.07 | 3.96 ± 1.11 | |
n | 6 | 6 | 8 |
Parameters measured to characterize the model confirm previous observations: the body weight was slightly reduced in SHRLN, kidney weight was not modified but 24h proteinuria and protein/creatinine ratio were increased indicating renal dysfunction. Left ventricular hypertrophy was visible in SHR but was more pronounced in SHRLN as shown by its normalized weight. Results are expressed as mean ± SEM.
Left ventricular hypertrophy was observed in both hypertensive groups as determined by length-normalized left ventricle weight. The SHR had larger left ventricles compared to those of WKY and those of SHRLN were larger than those of SHR. The data are shown in Table
The effect of L-NAME treatment on BP and short-term BP variability was evaluated in conscious rats used specifically for these measurements (n=8 SHR and n=9 SHRLN). L-NAME treatment increased BP in SHR. During the last week, 2 telemetered SHRLN died and others began to present slight decrease in blood pressure; thus only the 4 first weeks can be statistically analyzed. In SHR, SBP, DBP, PP, and their respective BPV were not modified during the 4 weeks. In SHRLN, SBP and DBP increased simultaneously with no change in PP. SBP BPV increased from day 14 with no change in DBP BPV, leading to a strong increase of PP BPV. (Figure
(a) time-evolution of systolic blood pressure (SBP, triangles), diastolic blood pressure (DBP, circles), and pulse pressure (PP, squares) in spontaneously hypertensive rat (SHR, grey symbols, and n=8) and in SHR during 5-week L-NAME treatment (SHRLN, black symbols, and n=9) and (b) short-term blood pressure variability as ARV (average real variability) are shown with similar symbols.
Basal blood pressure (MBP, SBP, and DBP) and pulse pressure (PP) were higher in SHR versus WKY and higher in SHRLN than in the two other groups. A similar pattern was observed for mean and diastolic diameters. Aortic stiffness was higher in SHR compared to that of WKY and L-NAME treatment leading to a greater increase in stiffness in SHRLN compared to SHR. This was demonstrated by increased
Thoracic aorta hemodynamics, diameter, and stiffness measurements.
Thoracic aorta | WKY | SHR basal | SHR | SHRLN basal | SHRLN | SHRLN |
---|---|---|---|---|---|---|
BP/WKY | BP/SHR | BP/WKY | ||||
Mean AP mmHg | 138 ± 6 | 190 ± 5 | 127 ± 6 | 229 ± 7 | 175 ± 11 | 138 ± 3 |
Systolic AP mmHg | 160 ± 6 | 223 ± 7 | 151 ± 7 | 274 ± 9 | 203 ± 12 | 161 ± 3 |
Diastolic AP mmHg | 122 ± 6 | 163 ± 4 | 107 ± 5 | 198 ± 6 | 154 ± 11 | 119 ± 2 |
Heart rate bpm | 380 ± 20 | 362 ± 14 | 269 ± 10 | 378 ± 11 | 306 ± 27 | 264 ± 19 |
Pulse pressure mmHg | 38 ± 1 | 61 ± 4 | 44 ± 3 | 77 ± 4 | 50 ± 2 | 42 ± 2 |
Local PWV m/s | 5.7 ± 0.1 | 8.9 ± 0.5 | 5.5 ± 0.4 | 13.6 ± 0.7 | 8.9 ± 0.8 | 6.4 ± 0.3 |
Mean diameter | 2517 ± 68 | 2856 ± 49 | 2691 ± 75 | 3060 ± 51 | 2897 ± 65 | 2853 ± 66 |
Diastolic diameter | 2390 ± 68 | 2756 ± 49 | 2499 ± 87 | 2981 ± 48 | 2808 ± 65 | 2732 ± 76 |
Aortic distension | 176 ± 9 | 136 ± 8 | 231 ± 16 | 80 ± 5 | 126 ± 19 | 179 ± 11# |
Aortic distension % | 7.4 ± 0.4 | 4.9 ± 0.3 | 9.3 ± 0.9 | 2.7 ± 0.1 | 4.5 ± 0.7 | 6.6 ± 0.6# |
Compliance 10−3mm2/kPa | 140.3 ± 6.4 | 78.4 ± 8.1 | 174.7 ± 16.8 | 39.6 ± 4.9 | 90.0 ± 15.6 | 145.8 ± 6.4 |
Distensibility 10−3/kPa | 29.4 ± 1.1 | 12.7 ± 1.4 | 32.7 ± 4.3 | 5.4 ± 0.6 | 14.3 ± 2.8 | 23.8 ± 2.1 |
Stiffness index | 3.9 ± 0.2 | 6.7 ± 0.6 | 4.0 ± 0.4 | 12.8 ± 0.9 | 7.3 ± 0.9 | 4.9 ± 0.4 |
AUCp/ms: pulse pressure | 16.3 ± 0.6 | 26.9 ± 1.5 | 20.3 ± 1.6 | 31.1 ± 1.4 | 20.6 ± 0.8 | 18.2 ± 1.0 |
AUCd/ms 10−1: distension | 3.7 ± 0.2 | 2.6 ± 0.2 | 5.0 ± 0.4 | 1.3 ± 0.1 | 2.2 ± 0.4 | 3.3 ± 0.3# |
distensibility index 10−2 | 22.9 ± 0.8 | 9.9 ± 1.0 | 25.3 ± 3.2 | 4.5 ± 0.5 | 11.0 ± 2.1 | 18.4 ± 1.5 |
(AUCd/AUCp) | ||||||
Compliance index | 23.9 ± 1.3 | 13.7 ± 1.3 | 23.5 ± 2.4 | 7.1 ± 0.6 | 13.6 ± 1.9 | 19.1 ± 1.6 |
n | 5 | 6 | 6 | 8 | 5 | 7 |
Parameters measured and calculated via the echotracking at the thoracic aorta. Results are expressed as mean ± SEM.
Mean blood pressure (MBP) and stiffness index are compared in the three groups of rats. Black bars: spontaneously hypertensive rats treated with L-NAME (SHRLN), grey bars: SHR without treatment, and white bars: normotensive WKY. Thoracic aorta (left graph) and abdominal aorta (right graphs) parameters are shown. A: SHRLN, parameters at basal pressure, and n= 8; B: SHRLN n=5, at BP matched with that of SHR n=6; C: both SHRLN n=7 and SHR n=6 at BP matched with that of WKY n=6. N are similar at TA and AA except n=5 for WKY at AA. One way ANOVA and Tukey posttest comparison:
Changes in pressure and diameter over time emphasized the difference between thoracic aorta (TA) and abdominal aorta (AA) stiffening in hypertensive rats with reduced NO (SHRLN). The dynamic pressure wave and diameter distension waves throughout the cardiac cycle are shown for SHRLN TA and AA at basal mean blood pressure (MBP), n=7 and 8, respectively, and at reduced MBP (after clonidine administration), n=5 for each site. BP levels are similar for TA and AA whereas only TA distension recovers when BP decreases. Bars on the right quantify these data via measuring the area under the curve (AUC adjusted to heart rate). Despite similar pulse pressures, only the thoracic aorta is shown to increase when blood pressure is reduced.
Under isobaric conditions, i.e., after decreasing BP and PP to that of WKY by administration of clonidine in SHR and SHRLN, we no longer observed differences in stiffness in the thoracic aorta between our three groups, demonstrating that the stiffness increase was strongly pressure-dependent. Distension remained slightly reduced in SHRLN compared to SHR at matched blood pressures (Table
The AA diameter was significantly smaller than the thoracic diameter in all groups. Also, all stiffness and distensibility parameters indicated significantly higher stiffness and lower compliance as expected at this more distal part of aorta.
The differences observed in the three groups at basal blood pressure were similar to those observed at the thoracic site: pressures, stiffness index, and local PWV were higher in the SHR compared to the WKY and more so in the SHRLN; distensibility, compliance index, and distension were lower in SHR than in WKY and lower in SHRLN compared to SHR.
However, in contrast to the thoracic aorta, after clonidine administration, the abdominal aorta of SHRLN remained stiffer under isobaric conditions (Table
Abdominal aorta hemodynamics, diameter, and stiffness measurements.
Abdominal aorta | WKY | SHR basal | SHR | SHRLN basal | SHRLN | SHRLN |
---|---|---|---|---|---|---|
BP/WKY | BP/SHR | BP/WKY | ||||
Mean AP mmHg | 139 ± 7 | 196 ± 4 | 134 ± 5 | 223 ± 8 | 195 ± 4 | 133 ± 2 |
Systolic AP mmHg | 164 ± 7 | 233 ± 6 | 160 ± 5 | 268 ± 11 | 230 ± 6 | 157 ± 2 |
Diastolic AP mmHg | 122 ± 7 | 166 ± 3 | 113 ± 5 | 192 ± 6 | 169 ± 4 | 116 ± 2 |
Heart rate bpm | 387 ± 15 | 368 ± 13 | 285 ± 7 | 368 ± 8 | 334 ± 20 | 270 ± 18 |
Pulse pressure mmHg | 42 ± 1 | 66 ± 4 | 47 ± 2 | 77 ± 5 | 60 ± 3 | 41 ± 2# |
Local PWV m/s | 7.6 ± 0.4 | 10.6 ± 0.5 | 7.5 ± 0.4 | 16.4 ± 1.2 | 15.1 ± 1.1 | 10.0 ± 0.8 |
Mean diameter | 1529 ± 45 | 1695 ± 17 | 1616 ± 53 | 1799 ± 34 | 1744 ± 42 | 1738 ± 39 |
Diastolic diameter | 1478 ± 45 | 1630 ± 22 | 1543 ± 58 | 1698 ± 34 | 1665 ± 59 | 1675 ± 46 |
Aortic distension | 72 ± 8 | 62 ± 4 | 88 ± 9 | 37 ± 5 | 31 ± 4 | 49 ± 8# |
Aortic distension % | 4.9 ± 0.6 | 3.8 ± 0.3 | 5.7 ± 0.6 | 2.2 ± 0.3 | 1.8 ± 0.3 | 3.0 ± 0.5# |
Compliance 10−3mm2/kPa | 30.7 ± 3.3 | 19.1 ± 1.7 | 36.3 ± 4.6 | 10.3 ± 1.3 | 10.5 ± 1.4 | 24.1 ± 3.0# |
Distensibility 10−3/kPa | 17.4 ± 1.6 | 8.7 ± 0.8 | 18.3 ± 2.2 | 4.3 ± 0.6 | 4.6 ± 0.7 | 10.8 ± 1.7# |
Stiffness index | 6.6 ± 0.7 | 9.3 ± 0.8 | 6.7 ± 0.5 | 20.4 ± 2.9 | 19.2 ± 3.2 | 12.5 ± 2.0 |
AUCp/ms: pulse pressure | 16.7 ± 0.6 | 29.0 ± 1.6 | 20.8 ± 1.1 | 30.5 ± 2.3 | 24.2 ± 1.8 | 16.0 ± 1.0# |
AUCd/ms 10−1: distension | 2.3 ± 0.3 | 1.9 ± 0.1 | 2.9 ± 0.3 | 1.1 ± 0.1 | 0.9 ± 0.1 | 1.4 ± 0.3# |
distensibility index 10−2 | 13.4 ± 1.2 | 6.7 ± 0.6 | 14.4 ± 1.8 | 3.6 ± 0.5 | 3.9 ± 0.6 | 8.7 ± 1.3# |
(AUCd/AUCp) | ||||||
Compliance index | 14.0 ± 1.0 | 9.8 ± 0.9 | 13.7 ± 1.2 | 5.7 ± 0.8 | 5.3 ± 0.9 | 8.5 ± 1.3 |
n | 5 | 6 | 6 | 8 | 5 | 7 |
Parameters measured and calculated via the echotracking at the thoracic aorta. Results are expressed as mean ± SEM.
This increase in stiffness in the SHRLN AA but not in TA under isobaric conditions was also made apparent by comparing diameter distension at both sites and both pressures (Figure
Furthermore, during clonidine administration, the higher stiffness and lower distensibility of the AA was maintained in SHRLN compared to SHR.
Wave analysis, quantified by the AUC corrected for HR (Tables
As for the other parameters, in contrast to AA, TA distension wave recovered and was no longer different from that in WKY after BP reduction. Again importantly the decrease in heart rate was similar at TA and AA levels and the AUC value corrected for heart rate.
The difference observed between AA and TA is emphasized by comparing BP and distension wave in SHRLN (Figure
The vascular wall thickness did not significantly differ between SHR and WKY but was increased in SHRLN compared to that of WKY and SHR. These observations were similar for TA and AA. The internal diameter was comparable in the three groups for the two sites. As expected AA diameter was much lower than TA diameter (-33 % in WKY, -41 % in SHR, and -33 % in SHRLN), in agreement with
Immunohistochemical characteristics of the TA and AA structures appear in Table
Aortic structure and composition.
Aortic site | Thoracic | Abdominal | ||||
---|---|---|---|---|---|---|
Group | WKY | SHR | SHRLN | WKY | SHR | SHRLN |
Thickness | | | | | | |
Lumen | | | | | | |
MCSA, AU | | | | | | |
MCSA /BW, mg/AU | | | | | | |
Elastic Lamellae, n | | | | | | |
Interlamellar Space, AU | | | | | | |
Colored Aortic Wall: | ||||||
(i) VSMC nucleus, % | | | | | | |
(ii) Collagen density % | | | | | | |
(iii) Elastin density % | | | | | | |
(iv) Collagen/elastin | | | | | | |
Stained Aortic Wall, %: | ||||||
(i) Fibronectin | | | | | | |
(ii) | | | | | | |
(iii) FAK | | | | | | |
n | 6 | 6 | 8 | 6 | 6 | 8 |
Results are expressed in percentage of colored or stained media area and reported as mean ± SEM.
Comparison of fibronectin (a) and collagen (b) accumulation in the thoracic (TA) and abdominal (AA) aorta between SHRLN n=8, SHR n=6, and WKY n=6. The data show that AA levels of fibrosis markers were specifically higher in AA from SHRLN in agreement with stiffness data
There were two important findings in the present study: (1) the major effects of chronic NO reduction in hypertensive rats were characterized by a greater increase in BP and aortic stiffening associated with structural changes in the aortic wall; (2) a specific pressure independent increase in AA stiffness compared to TA in the SHRLN which is associated with greater changes in fibrotic markers.
Large artery stiffening is now recognized as a cardiovascular risk factor as these compliant arteries lose their capacity to dampen the pulsatile force of cardiac systolic ejection. Increased blood pressure reduces arterial compliance but long-term high blood pressure as well as aging and chronic kidney disease induces moreover vascular wall remodeling which in turn further increases arterial wall stiffening in a vicious circle. Vascular wall remodeling involves alteration of numerous vascular wall components: increases in collagenous and fibrotic components, calcium deposition, reduction, and/or fragmentation of elastin and alteration of the vascular smooth muscle cells and is closely related to alteration of the endothelial cells and NO bioavailability. These mechanisms are complex and still not entirely understood [
Our previous study on SHR treated with the NO inhibitor L-NAME demonstrated a major role of endothelial dysfunction on the development of arterial stiffness. After just two weeks of treatment, the animals presented with increased BP, cardiac hypertrophy, renal dysfunction, increased BP variability, and severe aortic stiffening characterized by arterial remodeling. This severe hypertensive model presented similar features with both very old SHRs [
This first model experienced a significant degree of morbidity; thus it seemed prudent to increase the duration and decrease the concentration of L-NAME administration to improve animal outcomes and to better evaluate its structural and mechanical effects on aorta. In the present study we reduced the dose of L-NAME and increased the duration of the treatment to five weeks. As in the short protocol, we obtained comparable increases in BP and BP variability in conscious rats. We observed end organ damage and increased heart weight (normalized via tibia length) in the SHR compared to WKY and a further increase with L-NAME treatment. Proteinuria and the protein/creatinine ratio were significantly increased in SHRLN, indicating renal dysfunction.
These parameters allowed us to conclude that the five-week protocol is relevant for further studies on the role of NO reduction in vascular pathology and will be useful for both investigating the development of structural versus dynamic changes in the aorta and investigating the effects of therapeutic treatments on vascular stiffness.
Among the characteristics of the SHRLN model, BPV presents two further interests. First, the significant increase in BPV confirms the increase of intrinsic stiffness found in SHRLN as discussed below. Indeed, while several mechanisms may account for the BPV, the ability of the aorta to effectively buffer the pulsatile cardiac output is certainly a key component in regulating fluctuations in BP [
Second, despite correlated systolic and diastolic BP elevation, systolic but not diastolic BPV was parallelly increased throughout the duration of the treatment leading to a strong increase in PP variability. A similar pattern was observed in the short protocol and seems specific to this animal model [
The primary objective of this study was to, for the first time in this model, investigate the mechanostructural relationship of both the AA and TA in the same rats. We observed that the TA presented pressure-dependent stiffening, therefore disappearing when BP matched that of normotensive rats, in contrast to AA which presented both a pressure-independent and a remodeling-dependent stiffening; this is to say that arterial stiffness remained increased under normotensive isobaric conditions. This was shown via the usual parameters of compliance, distensibility and stiffness index measured at maximal systolic PP and distension. These findings are demonstrated in Figure
We recently compared AA and TA in a different model of hypertensive rats treated with a high salt diet [
As in the salt model, accumulation of fibronectin,
Fibrosis is generally considered as a major factor of remodeling and stiffening [
Several points regarding our methodology should be addressed although they have been largely discussed in our previous publication [
The thoracic site used between the diaphragm and the renal artery is often included in the abdominal aorta despite having diameter and compliance properties different from those of the abdominal infrarenal aorta. This site could have been alternatively named as the suprarenal aorta and our AA site the infrarenal aorta. The diaphragm is the limit between the thorax and the abdomen and by the way is often shown in anatomic schemes, as the limit between TA and AA but there no evidence that it is the functional and structural aortic limit. The difference between TA and AA embryologic development has not been related to the diaphragm. In human the length of the suprarenal but infradiaphragm is consistent and mainly called as superior abdominal aorta or suprarenal aorta; however a reduced vasa-vasorum, high incidence of aortic aneurysms, and reduced elastin level are described specifically for the infrarenal aorta [
In conclusion, the data presented give evidence that NO reduction, in addition to hypertension, induces fibrosis which reaches a high level in the abdominal aorta leading to a remodeling-dependent arterial stiffening.
Spontaneously hypertensive rat treated with L-Name
Abdominal aorta
Thoracic aorta
Pulse pressure
Nitric oxide
Blood pressure
Systolic blood pressure
Diastolic blood pressure
Mean blood pressure
Heart rate
Blood pressure variability
Focal adhesion kinase.
The data used to support the findings of this study are included within the article. The detailed data used to support the findings of this study are available from the corresponding author upon request.
The authors declare that they have no conflicts of interest.