Characterization of endothelium-dependent relaxations in mesenteries from transgenic hypertensive rats.
Endothelial dysfunction has been reported to be a feature of hypertension. We have investigated the relative contributions of nitric oxide (NO) and the endothelium-derived hyperpolarizing factor (EDHF) to endothelium-dependent relaxations in isolated mesenteries from (mREN-2)-27 transgenic hypertensive (TGH) rats and their normotensive controls (Hannover Sprague-Dawley). Relaxation to the endothelium-dependent relaxant, carbachol, was unimpaired in mesenteries from TGH rats compared to the Hannover Sprague-Dawley controls. Inhibition of NO synthase (with 100 microM Nomega-nitro-L-arginine methyl ester) had greater inhibitory effects against these relaxations in the mesenteries from Hannover Sprague-Dawley compared to TGH. Inhibition of EDHF activity with high K+ also had greater inhibitory effects against endothelium-dependent relaxations in the mesenteries from the Hannover Sprague-Dawley compared to TGH. The present results show that, although endothelium-dependent relaxation is unimpaired in mesenteries from TGH rats, there are differences in the relative contributions of NO and EDHF, such that inhibition of either NO or EDHF alone in TGH mesenteries has less impact compared to Hannover Sprague-Dawley. It is suggested that the recently identified reciprocal relationship between NO and EDHF is upregulated in the mesenteries from the TGH rats.
Randall
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MD
School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, UK. michael.randall@nottingham.ac.uk
March
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JE
D000818:Animals; D030801:Animals, Genetically Modified; D002217:Carbachol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D019806:Cromakalim / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D008729:Methoxamine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019806:Cromakalim; D009599:Nitroprusside; D011189:Potassium Chloride; D002217:Carbachol; D008729:Methoxamine; D019331:NG-Nitroarginine Methyl Ester