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We studied the renal vascular effects of flupenthixol and sulpiride isomers in the isolated perfused rat kidney in the presence of phenoxybenzamine (10(-5) M) and sotalol (10(-5) M). The vascular bed was contracted with prostaglandin F2 alpha (10(-7) -3 X 10(-6) M) and dose-dependently relaxed with dopamine. Cis-flupenthixol (10(-9)-10(-7) M) antagonized competitively the response to dopamine (apparent pA2 = 8.34 +/- 0.09; mean +/- SD) without affecting papaverine-induced relaxation. Trans-flupenthixol was without effect at 10(-7) M. The dopamine receptor antagonist activities of the sulpiride isomers are low and d-sulpiride is twice as active as 1-sulpiride. Thus, the renal vascular dopamine receptor can be further characterized by the relative antagonist activities of cis-flupenthixol and sulpiride and by a rather low stereospecificity in favor of d-sulpiride.

The distinction between a circulating renin-angiotensin system and a tissue renin-angiotensin system led us to determine tissue angiotensin converting enzyme (ACE) activity. This study establishes the experimental conditions for a good reproducibility of the fluorimetric assay of ACE and describes the use of [3H]ramiprilat to characterize ACE. Angiotensin converting enzyme activity was determined in rat lung, heart, aorta, and kidney (cortex and medulla) and in rabbit kidney (cortex, medulla, tubules, and glomeruli). ACE activity and [3H]ramiprilat binding does not increase in a linear fashion with the protein content of tissue extracts. Linearity limits varied from 1.0 to 2.0 mg of protein/ml (fluorimetry) and from 0.4 to 1.0 mg of protein/ml [( 3H]ramiprilat binding). Comparing ACE activity, measured by fluorimetry, with the amount of [3H]ramiprilat bound shows that the two techniques yield similar results.