Effect of NG-monomethyl L-arginine on endothelium-dependent relaxation in arterioles of one-kidney, one clip hypertensive rats.
Dose-response curves to topically applied acetylcholine, bradykinin, and nitroprusside were obtained by intravital microscopy in arcading arterioles of the spinotrapezius muscle of control (n = 9) and one-kidney, one clip hypertensive (1K1C) rats (n = 11) of 4 weeks' duration before and during superfusion with the specific inhibitor of nitric oxide formation NG-monomethyl L-arginine (LNMMA) (10(-4) M) and both LNMMA (10(-4) M) and indomethacin (2.8 x 10(-5) M). Resting arteriolar tone was higher in 1K1C rats than in controls, and vasodilation to acetylcholine and bradykinin, but not to nitroprusside, was reduced (p less than 0.05) in 1K1C rats compared with controls. LNMMA increased arteriolar tone (p less than 0.05) and inhibited the vasodilator responses to acetylcholine and bradykinin (p less than 0.05) in controls but not in 1K1C rats. LNMMA did not alter the response to nitroprusside in either group. Addition of indomethacin to LNMMA increased arteriolar tone and markedly reduced the response to bradykinin, but not to acetylcholine or nitroprusside, in both groups. These findings suggest that resting arteriolar tone is increased in 1K1C rats partially because of the decreased basal release or synthesis of nitric oxide. Responses to the endothelium-dependent vasodilators acetylcholine and bradykinin were attenuated in 1K1C rats, possibly because of changes in synthesis or release of nitric oxide for acetylcholine and of prostacyclin for bradykinin, because the response to the endothelium-independent vasodilator nitroprusside did not differ between the groups.
Nakamura
T
T
Department of Physiology, Eastern Virginia Medical School, Norfolk 23501.
Prewitt
R L
RL
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001160:Arterioles / Q000503:physiopathology*; D001920:Bradykinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine
D009599:Nitroprusside; D019323:omega-N-Methylarginine; D001120:Arginine; D000109:Acetylcholine; D001920:Bradykinin