AJP - Renal Physiology, Vol 260, Issue 5 695-F703, Copyright © 1991 by American Physiological Society
Insulin increases Na(+)-H+ exchange activity in proximal tubules from normotensive and hypertensive rats
F. A. Gesek and A. C. Schoolwerth
Department of Internal Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0160.
The effects of insulin on Na(+)-H+ exchange were examined in isolated
proximal segments from normotensive Sprague-Dawley (SD) and Wistar-Kyoto
(WKY) rats and spontaneously hypertensive rats (SHR), with monitoring of
rates of intracellular pH change (delta pHi/min) and ethylisopropyl
amiloride (EIPA)-suppressible 22Na+ uptakes. A 12-min insulin preincubation
was necessary for steady-state 22Na+ uptake and rate of pHi change. Insulin
responses were similar for 4-wk (prehypertensive) SHR and WKY tubules; 8-
(rising hypertension) and 16-wk (established hypertension) SHR responses
were increased (P less than 0.05) 23 and 36% with 10(-6) M insulin,
respectively. Insulin-like growth factors (IGF-I, IGF-II; 10(-10)-10(-7) M)
had no effect on Na(+)-H+ exchange activity. Incubation with physiological
concentrations of insulin in combination with hormones that stimulate
Na(+)-H+ exchange (angiotensin II; alpha-adrenoceptor agonists)
demonstrated no synergistic increases in SHR or WKY tubules; incubation
with hormones that inhibit Na(+)-H+ exchange [parathyroid hormone (PTH),
dopamine (DA)] indicated that insulin stimulation was decreased with PTH or
DA in WKY segments, but PTH or DA reduction of insulin stimulation was
lacking in SHR tubules. In summary, these data indicate a direct
stimulation by insulin of Na(+)-H+ exchange in the proximal nephron,
indicate an increased responsiveness in SHR compared with WKY tubules, and
suggest a modulatory role of insulin with other hormones in regulating
proximal nephron Na(+)-H+ exchange.
