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Central nervous system sites activated by renal pelvic epithelial sodium channels (ENaCs) in response to hypertonic saline and/or hypertonic potassium solution in awake rats

Grant number: 18/23157-6
Support type:Research Grants - Visiting Researcher Grant - International
Duration: February 17, 2019 - March 21, 2019
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Eduardo Colombari
Grantee:Eduardo Colombari
Visiting researcher: Mark Maurer Knuepfer
Visiting researcher institution: Saint Louis University (SLU), United States
Home Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated research grant:15/23467-7 - Experimental pathophysiology: role of central mechanisms of the cardiovascular and respiratory control changes induced by experimental hypertension and obesity, AP.TEM

Abstract

In some patients, renal nerve denervation has been reported to be an effective treatment for essential hypertension. That has been explained, in part, because of the reduction of the overactivation of the renin-angiotensin-aldosterone system. Interestingly, some research has shown that central aldosterone has an important regulatory function controlling the sympathetic output to the heart and kidneys. Recent studies show the presence of HSD2 (11²-Hydroxysteroid dehydrogenase type 2) cells in the nucleus of the solitary tract (NTS) in rat. Cells containing this specific enzyme are usually sensitive to aldosterone. Hence, researchers have successfully related their role in the central induction of sodium appetite in the presence of aldosterone. Yet, the role of central aldosterone in the neural control of renal function has not been studied. The neural control of renal sodium handling has been known for decades. Considerable evidence suggests that afferent renal nerves (ARN) and sodium balance play important roles in the development and maintenance of high blood pressure. ARN are sensitive to sodium concentrations in the renal pelvis. To better understand the role of ARN, we infused isotonic or hypertonic NaCl (308 or 500mOsm) into the left renal pelvis of conscious rats for two hours while recording arterial pressure and heart rate. Subsequently, brain tissue was analyzed for immunohistochemical detection of the protein Fos, a marker for neuronal activation. Fos-immunoreactive neurons were identified in numerous sites in the forebrain and brainstem. These areas included the nucleus tractus solitarius (NTS), the lateral parabrachial nucleus, the paraventricular nucleus of the hypothalamus (PVH) and the supraoptic nucleus (SON). The most effective stimulus was 500mOsm NaCl. Activation of these sites was attenuated or prevented by administration of benzamil (1¼M) or amiloride (10¼M) into the renal pelvis concomitantly with hypertonic saline. In anesthetized rats, infusion of hypertonic saline but not isotonic saline into the renal pelvis elevated ARN activity and this increase was attenuated by simultaneous infusion of benzamil or amiloride. We propose that renal pelvic epithelial sodium channels (ENaCs) play a role in activation of ARN and, via central visceral afferent circuits; this system modulates fluid volume and peripheral blood pressure. These pathways may contribute to the development of hypertension. (AU)