The collecting duct,dopamine and vasopressin‐dependent hypertension

AVP not only increases osmotic water permeability (P_f) in the rat cortical collecting duct (CCD), but also acts synergistically with aldosterone to augment sodium reabsorption (J_Na). These effects are inhibited by catecholamines via α₂ adrenergic receptors, and by dopamine. We review here studies designed to determine the mechanism and receptor involved in dopamine action. The inhibitory effect of dopamine on Na⁺ and water transport was found to be reversible, and was not produced by agonists specific to D_1A and D_1B receptors. D₂‐type (D₂, D₃ or D₄) receptors and activation of the GTP‐binding protein G_i were implicated by the observation that dopamine had no inhibitory effect when J_Na and P_f were stimulated by a cyclic AMP analogue plus isobutylmethylxanthine. The only dopaminergic antagonist that reversed the inhibitory effect of dopamine was clozapine, which is relatively D₄‐specific. We also found that dopamine or D₁‐specific agonists by themselves had no effect on cAMP production. However, dopamine inhibited the high rate of AVP‐dependent cAMP production, and this effect of dopamine was reversed by clozapine but not other antagonists or by inhibitors of protein kinase C. The D₄ receptor was observed in western blots of renal cortical proteins, and it was localized to the collecting duct by RT‐PCR and immuno‐histochemistry using a D₄‐specific antibody. These results show that at least a portion of the natriuretic effect of dopamine can be attributed to inhibition of AVP‐dependent Na⁺ reabsorption by the CCD, and they introduce another signalling system as a candidate in the aetiology of low‐renin, salt‐dependent hypertension.