BETA-ADRENERGIC-INDUCED LOCAL ANGIOTENSIN GENERATION IN THE RABBIT HIND-LIMB IS DEPENDENT ON THE KIDNEY

Evidence was sought for beta-adrenergic-induced increase in femoral vascular angiotensin production in sham-operated and nephrectomized rabbits. Systemic blood pressure and right femoral blood flow were monitored in anesthetized rabbits. Arterial and femoral venous plasma angiotensin II (Ang II) and angiotensin I (Ang I) were measured by radioimmunoassay after high-performance liquid chromatography. Isoproterenol, 1 and 10 nmol/min, was infused intrafemoral arterially, reducing femoral vascular resistance by 47 +/- 5% and 60 +/- 6% in the sham-operated group, and by 50 +/- 6% and 63 +/- 4% in the nephrectomized group, respectively. The hemodynamic effect of isoproterenol was blocked by 2-mu-mol/kg propranolol injected intravenously plus 0.2-mu-mol/min infused intrafemoral arterially, indicating that the effect was beta-adrenergically mediated. In the sham-operated group, arterial Ang II and Ang I levels were increased, respectively, by 85 +/- 16% and 103 +/- 23% with the low dose of isoproterenol, and by 121 +/- 13% and 563 +/- 126% with the high dose of isoproterenol. The apparent femoral Ang II secretion rate was increased by 3.2-fold and 4.4-fold, and the apparent femoral Ang I secretion rate increased by 4.3-fold and 21.2-fold, with the low and high dose of isoproterenol, respectively. Propranolol abolished or markedly attenuated the increased arterial angiotensin levels and the increased femoral angiotensin secretion rates. Neither the low nor the high dose of isoproterenol caused any increase in plasma levels or the apparent femoral secretion rates of the angiotensins in the nephrectomized group. Low plasma levels of Ang I and Ang II remained in the nephrectomized group, representing some locally generated angiotensins. These results indicate that isoproterenol, by acting on beta-adrenergic receptors, caused an increase of systemic and local angiotensin production, which depends on the presence of the kidney.