Regulation of renin secretion and expression in mice deficient in β1- and β2-adrenergic receptors

The present experiments were performed in β1/β2-adrenergic receptor-deficient mice (β1/β2ADR) to assess the role of β-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 β1/β2ADR 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 β1/β2ADR versus 692±59 in WT). A low-salt diet (0.03%) for 1 week increased plasma renin concentration significantly in both β1/β2ADR and WT mice (to 733±54 and 2789±555), whereas a high-salt diet (8%) suppressed it in both genotypes (to 85±24 in β1/β2ADR 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 β1/β2ADR 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 β-adrenergic receptor activation. In the chronic absence of β-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.