Nitric oxide synthase inhibition increases aortic stiffness measured by pulse wave velocity in rats

Objective: The present study was to examine whether endogenous nitric oxide (NO) plays a role in the regulation of vascular stiffness. Methods: Pulse wave velocity (PWV) was determined as the time delay between the foot of pr essure waves recorded simultaneously at the aortic arch and abdominal aorta (just above the bifurcation) in anesthetized Sprague-Dawley rats. A decrea se in vascular compliance results in an increase in PWV. Results: A bolus i njection of a NO synthase inhibitor, L-NAME (30 mg/kg), significantly incre ased PWV, accompanied by an increase in blood pressure. Since changes in bl ood pressure are known to affect PWV, phenylephrine (PE) was administered t o mimic the blood pressure changes induced by L-NAME, thus compensating for the pressure - dependent component of the PWV changes. At each given level of mean arterial pressure (MAP), PWV was significantly higher with L-NAME than with PE treatment, suggesting that acute withdrawal of endogenous NO r educes aortic compliance independent of changes in MAP. In rats chronically treated with L-NAME (0.5 g/l in drinking water) for 3 weeks, PWV was even higher than those acutely treated with L-NAME (at MAP = 150 mmHg). This add itional increase in vascular stiffness may be due to the remodeling of the vascular wall as a result of chronic NOS inhibition and hypertension. Concl usion: These data demonstrate that NO modulates vascular compliance indepen dent of blood pressure changes and that an intact endogenous NO system is r equired to maintain normal vascular compliance. (C) 2001 Elsevier Science B Y. All rights reserved.