Modulation of renal vasoconstrictor effect of NG-nitro-L-arginine in rabbit by angiotensin II and alpha-1 adrenergic receptor blockade.
Continuous production of endothelium-derived nitric oxide in peripheral vessels has been shown to modulate vascular resistance and blood pressure. By utilizing the substrate antagonist NG-nitro-L-arginine (NArg), we investigated the contribution of the renin-angiotensin or sympathetic nervous system to the renal vasoconstriction induced by nitric oxide synthase inhibition in anesthetized rabbits. In control experiments, an i.v. bolus of NArg (10 mg/kg) increased blood pressure from 100 +/- 2 to 108 +/- 3 mm Hg (P < .05) and decreased renal blood flow (RBF) and heart rate from 51 +/- 6 to 38 +/- 4 ml/min (27 +/- 7%, P < .05) and from 316 +/- 8 to 246 +/- 10 beats/min (P < .05), respectively. NArg decreased RBF significantly in animals pretreated with the angiotensin II (AII) antagonist losartan (Group II), or with the AII antibody KAA8 (Group IV). The RBF effect of NArg in antibody-treated rabbits, but not antagonist-treated animals, was comparable to that observed in the control group (Group I). Moreover, we observed that the renal vascular resistance effect of NArg was attenuated in losartan-treated rabbits vs. control animals. No such attenuation was observed in the KAA8-treated group. Furthermore, the administration of the alpha-1 adrenoceptor blocking agent prazosin did not attenuate the blood pressure, RBF and renal vascular resistance effects of NArg. Collectively, these results suggest that there is a greater involvement of vascular AII vs. circulating AII in the renal vasoconstrictor action of NArg. In addition, the results did not implicate the sympathetic nervous system in the renal vascular resistance effect of NArg in the anesthetized rabbit.
Hajj-Ali
A F
AF
DuPont Merck Pharmaceutical Company, Wilmington, Delaware.
Reilly
T M
TM
Wong
P C
PC
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004347:Drug Interactions; D006439:Hemodynamics / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D019808:Losartan; D008297:Male; D019335:Nitroarginine; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D013777:Tetrazoles / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D000906:Antibodies; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019335:Nitroarginine; D006830:Hydralazine; D001120:Arginine; D019808:Losartan; D011224:Prazosin