Abstract
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 in vivo study aimed to compare thoracic (TA) and abdominal (AA) aortic stiffness in the SHRLN (treated 5 weeks with L-NAME), SHR, and normotensive Wistar Kyoto (WKY). Dynamic properties of TA and AA were measured in the same rats, using echotracking recording of aortic diameter coupled with blood pressure (BP). Measurements were performed first at operating BP and then after BP reduction in hypertensive rats, thus in isobaric conditions. Histological staining and immunohistochemistry were used for structural analysis at both sites. At operating pressure, BP and pulse pressure (PP) were higher in SHRLN compared with SHR. Stiffness index was also increased and distensibility decreased in both TA and AA in SHRLN. At WKY-matched blood pressure, isobaric AA parameters remained specifically altered in SHRLN, whereas TA recovered to values identical to WKYs. Collagen, fibronectin, α5-selectin, and FAK were increased in SHRLN compared with SHR or WKY. Nevertheless, only the strong accumulations of fibronectin and collagen at the AA site in SHRLN were associated with intrinsic stiffening. In conclusion, we confirm that NO restriction associated with hypertension induces a severe pathological phenotype and shows that L-NAME induced stiffening is more pronounced in AA than in TA as a result of greater fibrosis.
Highlights
The stiffening of large central arteries occurs naturally with aging
In order to study the deleterious effect of NO bioavailability reduction, we developed a model of spontaneously hypertensive rats (SHR) treated with a moderate dose of nitric oxide synthase inhibitor L-nitroarginine methyl ester (LNAME) [12, 13]
We previously showed that this model leads to increased hypertension and an increase in aortic stiffness associated with aortic remodeling and fibrosis [13, 14]
Summary
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 [1] and kidneys [2]. A common feature of these factors which accelerate vascular aging is the reduction of nitric oxide (NO) availability [11], generally brought about by endothelial dysfunction and oxidative stress This loss of NO availability seems to both precede and be involved in a vicious cycle of vascular remodeling which leads to increased arterial stiffness. We previously showed that this model leads to increased hypertension and an increase in aortic stiffness associated with aortic remodeling and fibrosis [13, 14] This model develops cardiac ventricular hypertrophy as well as kidney damage and increased short-term blood pressure variability [15]. These induced features, which are characteristic of cardiovascular disease, were similar to those observed in old SHR [14]. This experimental model of severe hypertension seems relevant to investigate
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