[Vasodilator effect of nitric oxide is a necessary counter-regulation in the spontaneously hypertensive rat].
The chronic inhibition of NO-synthase by NG-nitro-L-arginine methyl ester (L-NAME, a L-arginine analogue) induces a dose-dependent decrease in aortic cGMP and an increase in blood pressure. We used this pharmacological approach to evaluate the release of NO in vivo in spontaneously hypertensive rats (SHR); 15 SHR and 10 Wistar-Kyoto rats (WKY) were given 25 mg L-NAME/kg/d by gavage for 15 days; 10 SHR and 10 WKY rats given water for the same period were used as control. During the trial, 10/15 SHR given L-NAME died. Systolic blood pressure (mmHg) increased from 132 +/- 6 to 170 +/- 4 in WKY given L-NAME and from 169 +/- 4 to 242 +/- 6 in SHR given L-NAME. Aortic cGMP content (fmol/mg protein) was 2,204 +/- 382 and 2,076 +/- 461 fmol/mg control WKY and SHR (NS), and was decreased to 324 +/- 44 and 641 +/- 70 in WKY and SHR given L-NAME respectively (p < 0.0001 each). L-NAME increased plasma atrial natriuretic factor only in SHR. In summary, basal aortic cGMP content, reflecting the basal release of NO, was similar in WKY and SHR. The decrease in aortic cGMP content of SHR given L-NAME, due to the blockade of NO-synthase, was accompanied by a large increase in systolic blood pressure and a tremendous mortality rate. Thus, basal release of NO is probably not impaired in SHR, but represents a major counterregulatory mechanism in this genetic model of arterial hypertension.
Arnal
J F
JF
INSERM U 367, Paris.
Battle
T
T
Ménard
J
J
Michel
J B
JB
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure; D001835:Body Weight; D006152:Cyclic GMP / Q000097:blood; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology*; D019001:Nitric Oxide Synthase; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects*
D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester