α-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% NaC10.2% 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 α-adrenergic receptors may be involved.