Studies of the role of endothelium-dependent nitric oxide release in the sustained vasodilator effects of corticotrophin releasing factor and sauvagine
| Autor: | D M, Barker, R, Corder |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Nitroprusside Nitric Oxide Synthase Type III Corticotropin-Releasing Hormone Peptide Hormones Vasodilator Agents Detergents Aorta Thoracic In Vitro Techniques Nitric Oxide Amphibian Proteins Potassium Chloride Glyburide Potassium Channel Blockers Animals Hypoglycemic Agents Endothelium Enzyme Inhibitors Rats Wistar omega-N-Methylarginine Dose-Response Relationship Drug Thiourea Tetraethylammonium Acetylcholine Mesenteric Arteries Rats Vasodilation NG-Nitroarginine Methyl Ester Papers Nitric Oxide Synthase Peptides Deoxycholic Acid |
| Zdroj: | British journal of pharmacology. 126(1) |
| ISSN: | 0007-1188 |
| Popis: | 1. The mechanisms of the sustained vasodilator actions of corticotrophin-releasing factor (CRF) and sauvagine (SVG) were studied using rings of endothelium de-nuded rat thoracic aorta (RTA) and the isolated perfused rat superior mesenteric arterial vasculature (SMA). 2. SVG was approximately 50 fold more potent than CRF on RTA (EC40: 0.9 +/- 0.2 and 44 +/- 9 nM respectively, P0.05), and approximately 10 fold more active in the perfused SMA (ED40: 0.05 +/- 0.02 and 0.6 +/- 0.1 nmol respectively, P0.05). Single bolus injections of CRF (100 pmol) or SVG (15 pmol) in the perfused SMA caused reductions in perfusion pressure of 23 +/- 1 and 24 +/- 2% that lasted more than 20 min. 3. Removal of the endothelium in the perfused SMA with deoxycholic acid attenuated the vasodilatation and revealed two phases to the response; a short lasting direct action, and a sustained phase which was fully inhibited. 4. Inhibition of nitric oxide synthase with L-NAME (100 microM) L-NMMA (100 microM) or 2-ethyl-2-thiopseudourea (ETPU, 100 microM) had similar effects on the vasodilator responses to CRF as removal of the endothelium, suggesting a pivotal role for nitric oxide. However the selective guanylate cyclase inhibitor 1H-[l,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ, 10 microM) did not affect the response to CRF. 5. High potassium (60 mM) completely inhibited the vasodilator response to CRF in the perfused SMA, indicating a role for K channels in this response. 6. Compared to other vasodilator agents acting via the release of NO, the actions of CRF and SVG are strikingly long-lasting, suggesting a novel mechanism of prolonged activation of nitric oxide synthase. |
| Databáze: | OpenAIRE |
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