Thiorphan-induced natriuresis in volume-expanded rats: roles of endogenous atrial natriuretic factor and kinins

Thiorphan, a potent inhibitor of enkephalinase (membrane metalloendopeptidase, atriopeptidase, EC 3.4.24.11) enhanced markedly (+214%) and prolonged the rise in plasma atrial natriuretic factor (ANF) immunoreactivity in anesthetized rats submitted to acute extracellular volume expansion obtained through i.v. injection of a Ringer's solution. These changes were accompanied by marked potentiations of the natriuretic and diuretic responses to the ANF-releasing stimulus, whereas kaliuresis was only slightly affected. Thiorphan also enhanced markedly the biphasic rise in urinary cyclic GMP excretion elicited by volume expansion. All these renal responses to volume expansion in thiorphan-treated rats were significantly reduced by pretreatment with anti-ANF antibodies, suggesting an involvement of the endogenous natriuretic hormone protected against degradation. However, pretreatment with antibradykinin antibodies led to qualitatively similar results, suggesting that the endogenous kinin-generating system in kidney may also participate in the responses to endogenous ANF and their potentiation by the peptidase inhibitor.