Agonist-sensitive calcium stores in arteries from steroid hypertensive rats.
The present study characterizes cellular calcium stores that are sensitive to norepinephrine and caffeine in arteries from deoxycorticosterone acetate hypertensive rats. Mesenteric arteries from normotensive and hypertensive rats were excised and cut into helical strips for isometric force recording. In calcium-free solution, phasic contractile responses to norepinephrine (5.9 x 10(-9) to 5.9 x 10(-6) M), but not caffeine (0.3-30 mM), were greater in hypertensive arteries. D-600, a calcium channel blocker, or removal of the endothelium did not alter phasic contractions to norepinephrine or caffeine. In contrast, contractions to both norepinephrine and caffeine were inhibited by ryanodine, a drug that depletes calcium from intracellular stores. An inhibitor of phospholipase C (2-nitro-4-carboxyphenyl N,N-diphenylcarbamate) attenuated contractions to norepinephrine but not those to caffeine. The augmented response to norepinephrine in hypertensive rats did not occur early after implantation of the mineralocorticoid, suggesting that this vascular change may not play a role in the development of high blood pressure in this experimental model. The augmented response to norepinephrine was reduced in mineralocorticoid-treated rats maintained on a low sodium diet, and these rats had blood pressures in the normotensive range. Because contractile responses to caffeine were not enhanced in arteries from hypertensive rats, we conclude that the cellular store for calcium is not enlarged compared with that in normotensive arteries. In contrast, the mobilization of calcium from cellular stores by norepinephrine is augmented in mineralocorticoid hypertension. This augmented response may be linked to altered phospholipase C activity and thus to an augmented action of inositol trisphosphate that releases calcium from intracellular sites.
Perry
P A
PA
Department of Physiology, University of Michigan Medical School, Ann Arbor.
Webb
R C
RC
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D003900:Desoxycorticosterone; D004032:Diet; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D014661:Vasoconstriction
D002110:Caffeine; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D002118:Calcium; D009638:Norepinephrine