Genetic control of renal thiazide receptor response to dietary NaCl and hypertension

Abstract

Excess NaCl increases blood pressure in some strains of animals but not others. An 8% NaCl diet did not change renal thiazide receptor (TZR) density in two salt-resistant normotensive rat strains (Wistar-Kyoto and Sprague-Dawley) [Fanestil, D. D., D. A. Vaughn, and P. Blakely. Am. J. Physiol. 273 ( Regulatory Integrative Comp. Physiol.42): R1241–R1245, 1997]. However, the renal response to salt differs in normal and hypertensive kidneys [Rettig, R., N. Bandelow, O. Patschan, B. Kuttler, B. Frey, and A. Uber. J. Hum. Hypertens. 10: 641–644, 1996]. Therefore, we examined two strains with salt-aggravated hypertension. Renal TZR did not change when Dahl-S (salt sensitive) animals became hypertensive with 8% dietary NaCl. In contrast, renal TZR decreased 34%, whereas blood pressure increased further, in SHR with 8% dietary NaCl. Blood pressure increased after N G-nitro-l-arginine in SHR, but renal TZR did not change, indicating the salt-induced decrease in TZR in SHR cannot be attributed nonspecifically to elevated arterial pressure. We conclude that the renal response to NaCl-induced increases in blood pressure can be genetically modulated independently of the genes that mediate either the primary hypertension or the salt sensitivity of the hypertension. This finding may be of use in future studies directed at identifying genotypes associated with salt-dependent hypertension.

Thiazide-Sensitive Cotransporter mRNA Expression Is Not Altered in Three Models of Hypertension

“…Since it is known that TSC inhibition results in increased Ca 2+ reabsorption in the distal tubule by a secondary mechanism [27], this observation suggested that hypercalciuria in SHR is due to an increased TSC function associated with a decreased Ca 2+ reabsorption by the distal tubule. Evidence for a potential implication of the thiazide receptor has also been obtained in another genetic model of hypertension [20], in Dahl salt-sensitive rats, in which the expected downregulation in thiazide receptors, when rats were switched from low-to high-salt diet, did not occur.…”

“…Thus, this study also suggests that the expression of TSC could be enhanced in SHR. In addition, Fanestil et al [20] have also reported that salt-sensitive Dahl rats fail to downregulate the thiazide receptor when the dietary salt intake was increased from 1 to 8%, suggesting that during high salt intake the TSC may increase salt reabsorption in the distal convoluted tubule as part of the hypertensive mechanism. All these data together suggest that the TSC may play a role in the development of hypertension in genetic models.…”