Canine renovascular responses to sumatriptan and 5-carboxamidotryptamine: modulation through endothelial 5-HT1-like receptors by endogenous nitric oxide.
1. In anaesthetized dogs, intra-left atrial (i.l.a.) administration of the 5-HT1-like receptor agonists, sumatriptan (1-10 micrograms kg-1) and 5-carboxamidotryptamine (0.03-0.3 micrograms kg-1) produced dose-related reductions in renal blood flow and vascular conductance, which were characterized by their rapid onset and recovery. 2. In these animals, i.v. administration of the inhibitor of nitric oxide (NO) synthase, NG-nitro-L-arginine methyl ester (L-NAME; 10 mg kg-1) significantly augmented the renal vasoconstrictor responses to i.l.a. sumatriptan and 5-carboxamidotryptamine. 3. The effects of L-NAME upon these responses to sumatriptan and 5-carboxamidotryptamine were significantly reversed by subsequent i.v. administration of L-arginine (1000 mg kg-1). 4. L-NAME significantly attenuated the systemic hypotensive responses to i.v. acetylcholine (0.3-3 micrograms kg-1) and this effect was also reversed by L-arginine. 5. L-NAME had no effect upon the renal vasoconstrictor response to i.l.a. administration of angiotensin II, nor did it affect the renal vascular conductance recovery response to brief mechanical occlusion of the renal artery. 6. These data suggest that sumatriptan and 5-carboxamidotryptamine stimulate the release of NO through the activation of a 5-HT1-like receptor located on the endothelial cells. 7. It is concluded that in canine renal vasculature, 5-HT1-like agonists (and presumably endogenous 5-hydroxytryptamine) can cause simultaneous activation of a 5-HT1-like receptor on both vascular smooth muscle and endothelial cells. The net renal vascular response to these agonists is therefore a function of both the vascular smooth muscle vasoconstriction and the concurrent vasodilator influence of NO released from the endothelium.
Whiting
M V
MV
Biology Division, Wellcome Research Laboratories, Beckenham, Kent.
Cambridge
D
D
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012077:Renal Artery / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*
D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D009569:Nitric Oxide; D012701:Serotonin; D018170:Sumatriptan; C047087:5-carboxamidotryptamine; D001120:Arginine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester