Vasopressin (ADH) and bradykinin (BK) have been shown to stimulate prostaglandin synthesis in rabbit cortical collecting tubules. We studied ADH and BK effects on osmotic water flow (L(p)), Na transport (J(Na)), and transepithelial voltage (V(T)). Bath BK but not lumen BK blunted subsequent ADH hydroosmotic responses. This BK effect was prevented by ibuprofen or pertussigen pretreatment and was overcome with exogenous cAMP, suggesting that BK, via prostaglandins, interferes with ADH action on L(p) at the cAMP generation step. In contrast. bath BK had no effect on bath-to-lumen (J(b-1)(Na)) or lumen-to-bath (J(1-b)(Na)) Na flux or on V(T). As reported by others aDH lowered J(1-b)(Na)) and depolarized V(T); however, prostaglandin synthesis inhibitors neither prevented nor reversed these ADH effects. Together, these BK and ADH data do not support regulation of J(Na) by peptide-stimulated prostaglandins. Moreover, cAMP alone depolarized V(T) but had no effect on J(1-b)(Na). Therefore, ADH-induced depolarization of V(T) may at least partly owe to cAMP effects on V(T) independent of accompanying changes in J(Na). As with L(p), bath BK blunted subsequent ADH effects on V(T) and, to a lesser extent, J(1-b)(Na); these BK effects on ADH action were also prevented by ibuprofen or pertussigen pretreatment. The data are consistent with the following model: 1) ADH depolarizes V(T) and increases L(p) via cAMP; 2) ADH decreases J(Na) via neither cAMP nor prostaglandins; and 3) BK, via prostaglandins, inhibits the actions of ADH on L(p) and V(T) at the inhibitory guanyl-nucleotide regulatory subunit of adenylate cyclase.
|Original language||English (US)|
|Journal||American Journal of Physiology - Renal Fluid and Electrolyte Physiology|
|State||Published - Jan 1 1985|
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