Calcium and contractile responses to phorbol esters and the calcium channel agonist, Bay K 8644, in arteries from hypertensive rats.
This study examined the calcium dependency of contractions in arteries from rats made hypertensive by aortic coarctation and in rats with genetic hypertensive (stroke-prone spontaneously hypertensive rats). Mesenteric artery and aortic strips were suspended in tissue baths for isometric force recording and contractions to two drugs were characterized: 1) a phorbol ester, TPA (12-O-tetrade-canoylphorbol-13-acetate), and 2) the calcium channel agonist, Bay K 8644. Thoracic aortae and mesenteric arteries from hypertensive rats were more sensitive to the contractile properties of the protein kinase C activator TPA than comparable arteries from normotensive rats. In thoracic aortae from coarcted rats, the contractile activity of Bay K 8644 was potentiated compared to normotensive values. In the presence of 19.2 mmol/L KCl, responses to Bay K 8644 in thoracic aortae from normotensive rats were potentiated and did not differ from coarcted values. In contrast, contractions to Bay K 8644 and TPA in abdominal aortae obtained below the coarctation were not different from normotensive values. Upon exposure to 26.2 mmol/L KCl, contractions to Bay K 8644 in abdominal aortae were potentiated and those in aortae from coarcted rats did not differ from sham values. Contractile responses to both drugs were blocked by nifedipine and verapamil and responses were attenuated in calcium-free solution. We conclude that calcium channel function and its regulation by protein kinase C contribute to altered vascular reactivity in hypertension. Further, these abnormalities have a pressure dependency, because they did not occur in abdominal aortae from coarcted rats.
Storm
D S
DS
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622.
Turla
M B
MB
Todd
K M
KM
Webb
R C
RC
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D015220:Calcium Channels; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium