ADRENERGIC REGULATION OF (NA+, K+)-ATPASE ACTIVITY IN PROXIMAL TUBULES OF SPONTANEOUSLY HYPERTENSIVE RATS

Increased renal nerve activity and sodium retention have been implicated in the development of hypertension in genetically transmitted forms of this disease. The present studies were designed to investigate the relationship between renal nerve integrity and renal proximal tubule (Na+, K+)-ATPase activity in spontaneously hypertensive rats (SHR). (Na+, K+)-ATPase activity of basolateral membranes (BLMs) enriched from proximal tubules of five-week-old SHR was greater, 328.6 ± 18.9 nmol Pi/mg protein · min, than in age-matched genetic controls rats (Wystar-Kyoto, WKY, rats), 262.3 ± 34.6 nmol P/mg protein · min (P < 0.02). There was no detectable difference in (Na+, K+)-ATPase activity of 13-week-old SHR and WKY rats. Prior renal denervation was associated with a reduction in proximal tubule basolateral membrane (BLM) (Na+, K+)-ATPase activity, 316.8 ± 23.8 to 223.1 ± 23.9 nmol Pi/mg protein/min (P < 0.02), in five-week SHR. However, denervation had no effect on renal (Na+, K+)-ATPase activity in either WKY rats, nor did sham-denervation in SHR. In addition, exogenous norepinephrine, 1 μM, produced a more pronounced stimulation of (Na+, K+)-ATPase activity in basolateral membranes from SHR as opposed to WKY controls (40.2% vs. 28.7%). Therefore, renal nerve integrity and exogenous catecholamines have a greater stimulatory influence on proximal tubule (Na+, K+)-ATPase activity in the early stages (prior to 5 weeks) of the development of hypertension in SHR than in age-matched WKY rats. These findings suggest that increased renal nerve activity and enhancement of proximal tubule (Na+, K+)-ATPase activity by catecholamines may contribute to salt retention and the development of hypertension in the SHR model of hypertension.