Chronic Reduction of Nitric Oxide Level in Adult Spontaneously Hypertensive Rats Induces Aortic Stiffness Similar to Old Spontaneously Hypertensive Rats

Abstract

Introduction: Age and hypertension are two major determinants of arterial stiffness, as well as endothelial dysfunction. The present study was designed to test whether a chronic reduction of endogenous nitric oxide (NO) produces arterial stiffening close to that observed in old spontaneously hypertensive rats (SHR), and also to study the effect of an acute or a chronic decrease in blood pressure (BP) on aortic distensibility. Methods: BP, aortic stiffness, endothelial dysfunction and remodelling were measured in male adult (20-week-old) SHR, in adult SHR treated with a nonspecific NO synthase inhibitor L-NAME (SHR/L-NAME) for 2 weeks, in adult SHR/L-NAME cotreated with perindopril (1 mg/kg/day) and in old SHR (55-week-old). Age-matched WKY were used as a normotensive group. Results: Aortic endothelial dysfunction, remodelling and stiffening appeared in old SHR. Reduction of NO production in adult SHR caused similar alterations. Acute decreases in BP in SHR/L-NAME did not improve isobaric aortic distensibility but a chronic reduction of BP prevented endothelial dysfunction, aortic remodelling and aortic wall stiffening. Conclusion: NO reduction in adult SHR induces aortic alterations similar to those observed during aging, which supports the major role of NO in the development of arterial stiffening. These aortic alterations can be prevented by angiotensin-converting enzyme inhibitor treatment.

Basal activity of voltage-gated Ca2+ channels controls the IP3-mediated contraction by α1-adrenoceptor stimulation of mouse aorta segments

“…Indeed, α 1 -adrenoceptor signaling, VSMC and endothelial Ca 2 þ signaling and VSMC NO sensitivity alter with aging (Madden et al, 2003), autophagy (Decuypere et al, 2011), hypertension (Abou-Saleh et al, 2013Giachini et al, 2009) and atherosclerosis (Ewart et al, 2014;. Moreover, VSMCs in cross-talk with endothelial cells, determine arterial mechanics (Zulliger et al, 2004), including the basal tonus of the blood vessel, and reduced nitric oxide (NO) bioavailability induces physiological alterations including arterial stiffness, vascular wall remodeling and hypertension (Isabelle et al, 2012;Leloup et al, 2014;Soucy et al, 2006). Both L-type Ca 2 þ channels blockers and basal NO release from elastic arteries reduce arterial stiffness (Safar, 2010), but the specific role of LCC in arterial (de-)stiffening needs further investigation.…”

Applanation Tonometry in Mice

“…Elevated aPWV caused by endothelial dysfunction was reported earlier in mice, 12,22 and several studies in rats indicate that the reduced bioavailability of nitric oxide is a key factor in the development of large artery stiffness. 7,8,12,24,25 It was also reported earlier that Nembutal-anesthetized WT mice have a lower PWV compared with WT mice sedated with other anesthetic agents. 10 In the present study, we were able to confirm these observations using applanation tonometry.…”

“…The fall in cfPWV observed here in eNOS −/− mice is in accordance with results shown before in rat. 25 …”

Differential Stiffening between the Abdominal and Thoracic Aorta: Effect of Salt Loading in Stroke-Prone Hypertensive Rats

“…The SHRSP presents with an increase in oxidative stress, a reduction in nitric oxide availability, and endothelial dysfunction [12, 13, 21, 25]. A decrease in nitric oxide bioavailability has been previously shown to induce strong aortic stiffening [17, 26]. Furthermore, since the SHRSP rats under a salted diet also present renal dysfunction [14] and renal dysfunction is commonly associated with increases in aortic stiffness [16, 27], we hypothesized that salt-sensitive SHRSP rats mimic hypertensive salt-sensitive humans and would therefore present with increased arterial stiffness.…”