Plasma Angiotensin in Binephrectomised Mice

Abstract

Plasma renin-angiotensin parameters were measured before and 24h after binephrectomy (BNx) in male Swiss (Ren-1, Ren-2) and BALB/c (Ren-1) female mice (representing the extremes of differences in tissue renin expression), together with in vivo inhibition of residual renin. Plasma Ang II increased from 18.9±7.3 to 48.1±16.9 pg/ml after BNx in conscious Swiss mice (±sd, p< 0.001, n = 11&12), renin activity (PRA) increased 2.76 times, angiotensinogen (aogen) increased 4.57 times and renin concentration (PRC) fell by 65%. In BALB/c, Ang II+Ang III decreased slightly (56.6±11 to 37.7±14.7, p< 0.05, n = 5&6), PRA was unchanged, aogen increased 12 times and PRC fell by 93%. Plasma ACE decreased by 26% and 28% respectively. Aogen did not increase further when post BNx plasma renin was inhibited with antirenin in vivo during 20h. Thus plasma angiotensin is maintained or considerably increased following BNx in mice and the change is consistent with first-order kinetics with respect to renin and aogen in the circulation. Whether the strain carries one or two renin genes, high renal and extra-renal renin production combined with a low plasma aogen phenotype yields resting angiotensin levels similar to other mammals. A kinetic regulation of aogen levels is proposed in mice wherein Ang I1 production is limited by low substrate concentration thereby ensuring normotension in the face of abundant extrarenal renin secretion.

Key Words:

• Renin-angiotensin system
• tissue renin
• renin kinetics
• angiotensinogen
• Ren-2 gene