Endothelin and nitric oxide mediate reduced myogenic reactivity of small renal arteries from pregnant rats.
We tested the hypothesis that endothelin acting through the endothelial ET(B) receptor subtype and the nitric oxide (NO) pathway accounts for reduced myogenic reactivity of the renal resistance vasculature during pregnancy. Small renal arteries (100-200 microm) were isolated from virgin and midterm pregnant rats when gestational renal hyperfiltration and vasodilation are maximal in this species. Myogenic reactivity (the adjustment of arterial diameter in response to a change in transmural pressure) was assessed with a pressurized myograph system. A rapid increase in transmural pressure from 60 to 80 mmHg resulted in a 2.4% diameter increase in vessels from virgin compared with an 8.1% increase in arteries from midgestation rats (n = 8 each, P < 0.05). Thus myogenic reactivity is markedly reduced during pregnancy. Incubation with the NO synthase inhibitors, an ET(B) receptor subtype antagonist (RES-701-1), the nonselective ET(A/B) receptor blocker (SB-209670), or endothelial removal abrogated the reduced myogenic reactivity of vessels from gravid rats without affecting myogenic reactivity in arteries from virgin animals. Thus the endothelium mediates the reduced myogenic reactivity of small renal arteries of midgestation rats most likely through the ET(B) receptor subtype and NO pathway.
Gandley
R E
RE
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh and Magee-Womens Research Institute, Pittsburgh, Pennsylvania 15213, USA. gandleyr+@pitt.edu
Conrad
K P
KP
McLaughlin
M K
MK
D000818:Animals; D016232:Endothelins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007189:Indans / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism; D012077:Renal Artery / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D016232:Endothelins; D004791:Enzyme Inhibitors; D007189:Indans; D010456:Peptides, Cyclic; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C087551:1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-; C087120:RES 701-1; D009599:Nitroprusside; D010656:Phenylephrine; D019335:Nitroarginine; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester