Alpha-adrenergic receptors and 45Ca2+ efflux in arteries from deoxycorticosterone acetate hypertensive rats.
Increased vascular sensitivity to catecholamines characterizes mineralocorticoid hypertension. The present study investigated three possible sites that may account for this abnormality: agonist affinity, Ca2+ release from intracellular stores, and Ca2+ sensitivity of the contractile proteins. Adult male Sprague-Dawley rats underwent uninephrectomy and were implanted subcutaneously with deoxycorticosterone acetate (DOCA; 200 mg/kg, 1% NaCl:0.2% KCl drinking water, 4-6 weeks). Control rats were sham treated. Helical strips of mesenteric arteries were placed in muscle baths for measurement of isometric force development. Although the ED50 for norepinephrine was significantly lower in arteries from DOCA rats (pD2, 8.21 +/- 0.15) than in those from sham controls (pD2, 7.24 +/- 0.11), agonist affinity, determined by partial blockade with phenoxybenzamine, did not differ between the two groups. In contrast, norepinephrine-stimulated 45Ca2+ efflux in the absence of extracellular Ca2+ was significantly greater in arteries from DOCA rats than in those from sham rats. In the presence of ryanodine to deplete intracellular Ca2+ stores, force development to Ca2+ was not different in saponin-permeabilized vessels from DOCA rats, indicating that the Ca2+ sensitivity of the contractile proteins was not altered in DOCA hypertension. We conclude that increased vascular sensitivity to norepinephrine in mineralocorticoid hypertension is related to increased release of Ca2+ from a subcellular store and not to changes in agonist affinity or to the contractile protein interaction. Based on previous reports, it is likely that this abnormality reflects a postreceptor change in signal transduction, but there is also evidence to suggest that an increase in the number of alpha-adrenergic receptors may be involved.
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Department of Physiology, University of Michigan, Ann Arbor 48109-0622.
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D000818:Animals; D001158:Arteries / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D002132:Calcium Radioisotopes; D011942:Receptors, Adrenergic, alpha; D003900:Desoxycorticosterone; D002118:Calcium