Regulation of renin secretion and expression in mice deficient in beta1- and beta2-adrenergic receptors.

The present experiments were performed in beta1/beta2-adrenergic receptor-deficient mice (beta1/beta2ADR(-/-)) to assess the role of beta-adrenergic receptors in basal and regulated renin expression and release. On a control diet, plasma renin concentration (in ng angiotensin I per mL per hour), determined in tail vein blood, was significantly lower in beta1/beta2ADR(-/-) than in wild-type (WT) mice (222+/-65 versus 1456+/-335; P<0.01). Renin content and mRNA were 77% and 65+/-5% of WT. Plasma aldosterone (in picograms per mL) was also significantly reduced (420+/-36 in beta1/beta2ADR(-/-) versus 692+/-59 in WT). A low-salt diet (0.03%) for 1 week increased plasma renin concentration significantly in both beta1/beta2ADR(-/-) and WT mice (to 733+/-54 and 2789+/-555), whereas a high-salt diet (8%) suppressed it in both genotypes (to 85+/-24 in beta1/beta2ADR(-/-) and to 676+/-213 in WT). The absolute magnitude of salt-induced changes of plasma renin concentration was markedly greater in WT mice. Acute stimulation of renin release by furosemide, quinaprilat, captopril, or candesartan caused significant increases of plasma renin concentration in both beta1/beta2ADR(-/-) and WT mice, but again the absolute changes were greater in WT mice. We conclude that maintenance of normal levels of renin synthesis and release requires tonic beta-adrenergic receptor activation. In the chronic absence of beta-adrenergic receptor input, the size of the releasable renin pool decreases with a concomitant reduction in the magnitude of the plasma renin concentration changes caused by variations of salt intake or acute stimulation with furosemide, angiotensin-converting enzyme, or angiotensin type 1 receptor inhibition, but regulatory responsiveness is nonetheless maintained.