CHLOROTYROSINE EXERTS RENAL EFFECTS AND ANTAGONIZES RENAL AND GASTRICRESPONSES TO ATRIAL-NATRIURETIC-PEPTIDE

3-Chloro-L-tyrosine (3CT) is an inhibitor of tyrosine hydroxylase, the rate-limiting enzyme for catecholamine synthesis. In vivo inhibition of tyrosine hydroxylase results in lower catecholamine levels. 3CT (0. 5 mg/kg), administered as a bolus i.v. to anesthetized uninephrectomiz ed rats, elicited increases of 72% and 44% in urinary sodium concentra tion and volume, respectively, whereas a dose of 1 mg/kg caused increa ses of 27% and 29%. 3CT, 1 mg/kg, resulted in a 2-fold increase in pla sma aldosterone (ALD); 0.5 mg/kg was without significant effect. At a dose of 1 mg/kg 3CT significantly antagonized the renal effects of atr ial natriuretic peptide (ANP) (1.5 mu g kg(-1) min(-1) by intrarenal i nfusion), expressed as an enhanced excretion of urine volume (102 +/- 14 vs. 70 +/- 11 mu l/min) and sodium (16.1 +/- 1.8 vs. 11.5 +/- 1.7 m u Eq/min) and increased osmolar clearance (171 +/- 12 vs. 144 +/- 13 m u l/min). A dose of 0.5 mg/kg of 3CT did not produce these same respon ses to ANP. The increased urine flow caused by 3CT may reflect reduced norepinephrine synthesis. The inverse dose-effect relationship of 3CT on urine flow rate may result from concomitant depletion of dopamine (DA) and elevated circulating ALD. The antagonism of 3CT on responses to ANP is not at the receptor level, because 3CT did not compete for [ I-125] ANP binding or inhibit ANP-stimulated guanylate cyclase in kidn ey cell membranes. It was proposed that the reduced basal sympathetic and renal DA tone, together with the elevated ALD level, account for t his antagonism. Furthermore, 3CT antagonized ANP in another system: 3C T given i.p. at doses of 0.1, 0.2 and 0.5 mg/kg antagonized gastric ac id secretion in response to ANP given i.c.v.