Male-female differences in the relative contribution of endothelial vasodilators released by rat tail artery.
Several different vasodilator substances can be released by vascular endothelium in response to mechanical stimuli and vasoactive agents. The purpose of this study was to determine whether there is a male-female difference in the relative contributions of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) to endothelium-dependent vasodilation. Perfusion pressure was measured in isolated tail arteries from male and female rats. Vasodilators released by mechanical shear stress were assessed by constricting the artery with methoxamine; acetylcholine was applied to induce receptor-mediated vasodilation. We used an inhibitor of NO synthase, N(G)-monomethyl-L-arginine acetate (L-NMMA), and elevated levels of K(+) (27 mM) to reveal the relative contributions of NO and EDHF, respectively. Indomethacin was present in all experiments to block prostanoid production. The results indicate that NO was the primary vasodilator released by male tail arteries in response to both mechanical stress and acetylcholine (the L-NMMA-sensitive component of the combined L-NMMA/K(+) effect was 83 +/- 8% and 101 +/- 4%, respectively). However female tail arteries appeared to utilize both NO and EDHF for vascular relaxation (e.g., L-NMMA sensitivity: 58 +/- 9%; K+-sensitivity: 42 +/- 9% in mechanical stress experiments). These findings suggest endothelial regulation differs between males and females.
Department of Pharmacology, College of Medicine, University of California, Rm. 360, Med. Sure II, Irvine, 92697-4625, USA.
Kirk J
KJ
Pak
Greg G
GG
Geary
Sue P
SP
Duckles
Diana N
DN
Krause
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000502:physiology*; D001685:Biological Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D011464:Epoprostenol / Q000037:antagonists & inhibitors / Q000502:physiology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D010477:Perfusion; D010812:Physical Stimulation; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012039:Regional Blood Flow / Q000502:physiology; D012727:Sex Characteristics; D013623:Tail / Q000098:blood supply; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001685:Biological Factors; D011448:Prostaglandin Antagonists; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D008729:Methoxamine; D000109:Acetylcholine; D007213:Indomethacin