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 pressure waves recorded simultaneously at the aortic arch and abdominal aorta (just above the bifurcation) in anesthetized Sprague-Dawley rats. A decrease in vascular compliance results in an increase in PWV.


RESULTS
A bolus injection of a NO synthase inhibitor, L-NAME (30 mg/kg), significantly increased PWV, accompanied by an increase in blood pressure. Since changes in blood pressure are known to affect PWV, phenylephrine (PE) was administered to 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 reduces 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 additional increase in vascular stiffness may be due to the remodeling of the vascular wall as a result of chronic NOS inhibition and hypertension.


CONCLUSIONS
These data demonstrate that NO modulates vascular compliance independent of blood pressure changes and that an intact endogenous NO system is required to maintain normal vascular compliance.
Fitch
R M
RM
Department of Pharmacology, Berlex Biosciences, P.O. Box 4409, 15049 San Pablo Avenue, Richmond, CA 94804-0099, USA.
Vergona
R
R
Sullivan
M E
ME
Wang
Y X
YX
D000704:Analysis of Variance; D000818:Animals; D001012:Aorta, Abdominal; D001013:Aorta, Thoracic; D004730:Endothelium, Vascular / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester