Endothelial dysfunction in aortic rings and mesenteric beds isolated from deoxycorticosterone acetate hypertensive rats: possible involvement of protein kinase C

• Published in: European journal of pharmacology Vol. 494; no. 2; pp. 199 - 204
• Main Authors: Fatehi-Hassanabad, Zahra, Fatehi, Mohammad, Shahidi, Mohsen Imen
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 28-06-2004; Elsevier
• Subjects: Acetylcholine - pharmacology; Alkaloids; Anesthesia; Animals; Aorta; Aorta, Thoracic - enzymology; Aorta, Thoracic - physiopathology; Arterial hypertension. Arterial hypotension; Benzophenanthridines; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Blood Pressure - physiology; Body Weight - drug effects; Body Weight - physiology; Calphostin C; Cardiology. Vascular system; Chelerythrine; Desoxycorticosterone; Dose-Response Relationship, Drug; Endothelium, Vascular - enzymology; Endothelium, Vascular - physiopathology; Enzyme Inhibitors - pharmacology; Experimental diseases; Heart - drug effects; Heart Rate - drug effects; Hypertension; Hypertension - chemically induced; Hypertension - enzymology; Hypertension - physiopathology; In Vitro Techniques; Male; Medical sciences; Mesenteric vascular bed; Naphthalenes - pharmacology; Nitroprusside - pharmacology; Organ Size - drug effects; Organ Size - physiology; Phenanthridines - pharmacology; Phenylephrine - pharmacology; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - physiology; Rats; Rats, Sprague-Dawley; Splanchnic Circulation - drug effects; Splanchnic Circulation - physiology; Vasodilator Agents - pharmacology; Hypertension; Aorta; Calphostin C; Mesenteric vascular bed; Chelerythrine; Protein kinase C; Rat; Enzyme; Transferases; Rodentia; Cardiovascular disease; Hypertension: Aorta; Artery; Endothelium; Vertebrata; Mesenteric artery; Vasomotricity; Mammalia; Animal; Blood vessel; Circulatory system
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2004.05.012

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 μM) 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.