NG-monomethyl-L-arginine and nitroarginine potentiate pressor responsiveness of vasoconstrictors in conscious rats.
NG-monomethyl-L-arginine (NMA) and nitroarginine have been reported to be competitive inhibitors of the production of endothelium-derived relaxing factor (EDRF). In chronically instrumented conscious rats, we observed that the pressor response of NMA was attenuated by pretreatment with L-arginine but not by pretreatment with D-arginine, phentolamine, or meclofenamate. Inhibitors of the renin-angiotensin system, captopril and [Sar1,Ile5,Thr8]angiotensin II, did not significantly affect the pressor response of NMA, either. Ten to fifteen minutes after bolus administration of 7-15 mg/kg NMA, when baseline blood pressure was virtually restored, the pressor responses of angiotensin II (ANG II), norepinephrine, and arginine vasopressin were significantly potentiated by approximately 30-40% compared with control values. This potentiation was prevented by pretreatment with L- but not D-arginine. It was also observed in conscious rats subjected to ganglionic blockade. Likewise, the pressor responses of ANG II were significantly increased during infusions of 2 and 5 micrograms/min nitroarginine methyl ester (NAME), dosages that raised baseline blood pressure by 6 +/- 2 and 15 +/- 3 mmHg, respectively. During administration of 5 and 50 micrograms/min NAME, hypotensive responses of methacholine and histamine were only modestly attenuated compared with the responses recorded during infusions of phenylephrine, which raised resting blood pressure to comparable levels. Finally, in freshly isolated rat aorta, NMA inhibited basal and stimulated production of guanosine 3',5'-cyclic monophosphate in a manner comparable to reduced hemoglobin, a known inhibitor of EDRF.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology, University of New Mexico School of Medicine, Albuquerque 87131.
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Whittemore
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D006152:Cyclic GMP / Q000096:biosynthesis; D004357:Drug Synergism; D005260:Female; D019331:NG-Nitroarginine Methyl Ester; D019335:Nitroarginine; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine
D000317:Adrenergic alpha-Antagonists; D014662:Vasoconstrictor Agents; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D001120:Arginine; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester