The vasodilatory effect of endogenous nitric oxide is a major counter-regulatory mechanism in the spontaneously hypertensive rat.
OBJECTIVE
A decreased responsiveness to endothelium-dependent vasodilatory substances is characteristically seen in isolated arteries from spontaneously hypertensive rats (SHR). However, the precise status and role of nitric oxide (NO), which is, at least in part, the endothelium-derived relaxing factor, remains unclear in SHR. The objective of the present study was to evaluate the importance of NO release in vivo.


METHODS
The effect on systolic blood pressure of chronic administration of NG-nitro-L-arginine methyl ester (L-NAME, an NO-synthase inhibitor) was studied. Twenty SHR and 10 Wistar-Kyoto (WKY) rats were given 25 mg/kg per day L-NAME by gavage. Thirteen SHR and 14 WKY rats given water for the same period were used as controls. Rats were killed after 15 days and the aortic wall cyclic GMP (cGMP, the second messenger of NO) and cGMP-dependent kinase (the effector of cGMP) concentrations were assessed.


RESULTS
During the trial, 11 of the 20 SHR given L-NAME died. Mean +/- SD systolic blood pressure increased from 131 +/- 8 to 171 +/- 10 mmHg in WKY rats given L-NAME and from 185 +/- 10 to 249 +/- 22 mmHg in SHR given L-NAME. Aortic cGMP content was similar in control WKY rats (2122 +/- 707 fmol/mg protein) and in control SHR (2098 +/- 704 fmol/mg protein), and was decreased in the L-NAME-treated WKY rats and SHR to 308 +/- 87 and 644 +/- 222 fmol/mg protein, respectively. The aortic concentrations of cGMP-dependent kinase were not different in any group.


CONCLUSIONS
Basal release of NO does not appear to be impaired in SHR, but represents a major counter-regulatory mechanism in this genetic model of arterial hypertension.
Arnal
J F
JF
INSERM Unit 367, Paris, France.
Battle
T
T
Ménard
J
J
Michel
J B
JB
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure; D006152:Cyclic GMP / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D009929:Organ Size; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation
D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester