Endothelial dysfunction in aortic rings and mesenteric beds isolated from deoxycorticosterone acetate hypertensive rats: possible involvement of protein kinase C.
The main objectives of this study were to investigate the effects of deoxycorticosterone acetate (DOCA)-induced hypertension on the aortic and mesenteric vascular responses to vasodilator and vasoconstrictor agents and also to elucidate whether protein kinase C (PKC) was involved in these responses, by using chelerythrine and calphostin C, the inhibitors of protein kinase C. Hypertension was induced in male Sprague-Dawley rats (200-250 g) by DOCA-salt injection [20 mg/kg, twice weekly for 5 weeks, subcutaneously (s.c.)] and NaCl (1%) was added to their drinking water. Control rats received a saline injection (0.5 ml/kg, twice weekly for 5 weeks, s.c.), then the animals were anaesthetised [thiopental, 30 mg/kg, intraperitoneally (i.p.)] and the arterial blood pressure was measured. Mean arterial blood pressure in control and hypertensive rats were 98+/-7.5 and 163+/-3.5 mmHg, respectively (P<0.0001). In the in vitro studies, rings of descending aorta and mesenteric beds were precontracted with phenylephrine and then concentration-response curves to acetylcholine and sodium nitroprusside were constructed. In the tissue removed from hypertensive rats, the responses to acetylcholine, but not to sodium nitroprusside, were significantly reduced. However, addition of chelerythrine (10 microM) or calphostin C (100 nM) to the organ bath significantly restored these impaired responses. Our data suggest that protein kinase C plays a crucial role in the endothelial dysfunction induced by hypertension.
Fatehi-Hassanabad
Zahra
Z
Department of Physiology and Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, P.O. Box 91775 1843, Meshed, Iran. z_fatehi@yahoo.com
Fatehi
Mohammad
M
Shahidi
Mohsen Imen
MI
D000109:Acetylcholine / Q000494:pharmacology; D000470:Alkaloids; D000758:Anesthesia; D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology / Q000503:physiopathology; D053119:Benzophenanthridines; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003900:Desoxycorticosterone; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000201:enzymology / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D010617:Phenanthridines / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D010617:Phenanthridines; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D003900:Desoxycorticosterone; C016299:chelerythrine; D011493:Protein Kinase C; C058819:calphostin C; D000109:Acetylcholine