This research is directed at determining the pattern of hormone response that governs the Na+ transport properties of the cortical collecting duct (CCD) from prehypertensive spontaneously hypertensive rats (SHR), and Wistar Kyoto rats (WKY). Among the hormone effects to be examined will be the interaction between aldosterone and vasopressin (AVP) in stimulating Na+ reabsorption and the inhibitory potential of alpha2-adrenergic agonists, bradykinin, and atrial natriuretic peptide. It has been demonstrated that the Sprague-Dawley rat CCD responds to AVP with a rapid and sustained increase in net NaCl absorption due to an enhancement of Na+ entry across the luminal membrane via amiloride inhibitable, conductive channels. This stimulatory effect of AVP is potentiated by aldosterone. These results suggest a rationale for the requirement of vasopressin in some models of hypertension because the two could interact to cause salt retention. It is presently unknown whether there is any effect of AVP alone, or if there is an additive effect of AVP with aldosterone on the CCD of SHR or WKY rats. About 150 male, pathogen-free, SHR rats and 50 male, pathogen-free, WKY rats per year will be the source of the cortical collecting ducts. Approximately half of each strain will receive subcutaneous implants of aldosterone (the other half will be anesthetized and implanted with pellets collecting tubules. The standard isolated perfused tubule technique will be used to study the alterations in unidirectional lumen-to-bath isotopic Na+ flux and changes in transepithelial voltage when the various hormones and autacoids listed above are added to the bathing solution. To further characterize the mechanisms of Na+ transport, amiloride will be added to the perfusate. This will indicate the fraction of he observed Na+ flux which occurs through an amiloride-sensitive, electrogenic pathway versus a putative electroneutral cotransport pathway or by free diffusion through the paracellular pathway.
| Hawk, C T; Li, L; Schafer, J A (1996) AVP and aldosterone at physiological concentrations have synergistic effects on Na+ transport in rat CCD. Kidney Int Suppl 57:S35-41 |
| Kudo, L H; Hawk, C T; Schafer, J A (1994) Sodium and water transport in cortical collecting duct of Dahl salt-resistant rat. Am J Physiol 267:F583-91 |
| Hawk, C T; Schafer, J A (1993) Clonidine, but not bradykinin or ANP, inhibits Na+ and water transport in Dahl SS rat CCD. Kidney Int 44:30-5 |
| Schafer, J A; Hawk, C T (1992) Regulation of Na+ channels in the cortical collecting duct by AVP and mineralocorticoids. Kidney Int 41:255-68 |
