Haemodynamic responses to NG-monomethyl-L-arginine in spontaneously hypertensive and normotensive Wistar-Kyoto rats.
1. Nitric oxide (NO) is a major component of endothelium-derived relaxing factor (EDRF) the synthesis of which from L-arginine can be inhibited by NG-monomethyl-L-arginine (L-NMMA). To assess whether basal NO tone is different in experimental hypertension, the haemodynamic effects of L-NMMA have been compared in anaesthetized spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats in which autonomic reflexes were blocked by ganglion blockade. 2. Bolus intravenous injections of L-NMMA, 1-30 mg kg-1, but not D-NMMA, 1-30 mg kg-1, induced dose-related increases in mean arterial pressure and decreases in conductances in the renal, carotid, hindquarters and mesenteric vascular beds in both SH and WKY rats. Although the different vascular beds varied in their maximum responses to L-NMMA, there were neither qualitative nor quantitative differences between the two rat strains in this respect. 3. The effects of L-NMMA, 30 mg kg-1, i.v. on all parameters were rapidly and completely reversed by L-arginine, 30 mg kg-1, i.v., in both SH and WKY rats. 4. The results indicate that NO derived from L-arginine exerts a powerful vasodilator tone in both anaesthetized, ganglion-blocked SH and WKY rats. Although NO appears to contribute differentially to tone in the different vascular beds, there were no major differences between the two rat strains in this respect. Hence a reduced NO tone to the vasculature is unlikely to be a major factor contributing to the elevated blood pressure in the adult SH rat.
Fozard
J R
JR
Preclinical Research, Sandoz Pharma AG, Basel, Switzerland.
Part
M L
ML
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013237:Stereoisomerism; D014655:Vascular Resistance / Q000187:drug effects; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D001120:Arginine