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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Neonatal sympathectomy reduces NADPH oxidase activity and vascular resistance in spontaneously hypertensive rat kidneys

Institutes of ¹Physiology and ²Pathology, University of Greifswald, Greifswald, Germany

Submitted 12 January 2006 ; accepted in final form 9 March 2006

Neonatal sympathectomy reduces arterial pressure in spontaneously hypertensive rats (SHR). In SHR transplanted with a kidney from sympathectomized SHR, arterial pressure was lower and less Na⁺ sensitive than in SHR transplanted with a kidney from hydralazine-treated SHR. This study was performed to identify underlying renal mechanisms. Tests for differential renal mRNA expression of nine a priori selected genes revealed robust differences for renal medullary expression of the NADPH oxidase subunit p47^phox. Therefore, we investigated the effects of neonatal sympathectomy on renal mRNA expression of NADPH oxidase subunits, NADPH oxidase activity, and renal function. In 10-wk-old sympathectomized SHR fed a 0.6% NaCl diet, medullary p47^phox and gp91^phox expression was 40% less than in hydralazine-treated SHR. Also, after a 1.8% NaCl diet, medullary p47^phox mRNA expression was lower in sympathectomized than in hydralazine-treated SHR. We found lower cortical (–30%, P < 0.01) and medullary (–30%, P < 0.05) NADPH oxidase activities in sympathectomized than in hydralazine-treated or untreated SHR. Glomerular filtration rate, renal blood flow, medullary blood flow, and fractional Na⁺ excretion in kidney grafts from sympathectomized and hydralazine-treated donors (n = 8 per group) were similar at baseline and in response to a 20-mmHg rise in renal perfusion pressure. Renal vascular resistance was lower in kidneys from sympathectomized than hydralazine-treated donors (25 ± 2 vs. 32 ± 4 mmHg·min·ml^–1, P < 0.05). The results indicate that the sympathetic nervous system contributes to the level of renal NADPH oxidase activity and to perinatal programming of alterations in renal vascular function that lead to elevated renal vascular resistance in SHR.

inbred strains; kidney; sympathetic activity; gene expression

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