Endothelium-derived relaxing factor influences renal vascular resistance.
The mechanism of action of different vasodilators was investigated in the isolated perfused kidney of the rat. Acetylcholine (ACh, 10 nM-1 microM) and ATP (10 nM-1 microM), compounds known to relax isolated arteries in an endothelium-dependent fashion, caused concentration-dependent decreases in renal vascular resistance (RVR). Also, the endothelium-independent vasodilators verapamil (100 nM-10 microM), glyceryl trinitrate (GTN, 1-100 microM), and sodium nitroprusside (SNP, 1-100 microM) reduced RVR concentration dependently. Gossypol (10 microM, 5 min), an inhibitor of endothelium-derived relaxing factor (EDRF) production and/or release, increased basal RVR by 5% and significantly inhibited the vasodilator effects of ACh and ATP but had no effect on verapamil- or GTN-induced decreases in RVR. Methylene blue (MB) increased RVR dose dependently by up to 50%. About 50% of this effect could be antagonized with phentolamine (1 microM). MB abolished the relaxant response to ATP and attenuated the response to ACh. The dose-response curve of SNP was shifted to the right, and the relaxation to verapamil was slightly reduced. L-NG-methylarginine (100 microM) increased RVR by approximately 20%, and this effect was completely reversed by L-arginine (1 mM). N omega-nitro-L-arginine (100 microM) increased RVR by approximately 40% and attenuated the response to ATP but had no effect on the SNP-induced decrease in RVR. These results suggest that EDRF plays an important role in the regulation of RVR.
Radermacher
J
J
Department of Clinical Pharmacology, Hannover Medical School, Federal Republic of Germany.
Förstermann
U
U
Frölich
J C
JC
D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004008:Diclofenac / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D006072:Gossypol / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000098:blood supply / Q000502:physiology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology
D011453:Prostaglandins; D004008:Diclofenac; D009599:Nitroprusside; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D001120:Arginine; D014700:Verapamil; D005996:Nitroglycerin; D006072:Gossypol; D000109:Acetylcholine; D008751:Methylene Blue