INTERRELATION BETWEEN BARORECEPTOR AND MACULA DENSA MECHANISMS IN THE CONTROL OF RENIN SECRETION

1. It was the aim of this study to examine the interrelation between 'baroreceptor' function and the macula densa signal in the control of renin secretion from the kidneys. To this end we investigated the effects of frusemide and bumetanide, two different inhibitors of the macula densa Na+-K+-2Cl-cotransport, on pressure-dependent renin release from isolated perfused rat kidneys. In addition, pressure modulation of renin secretion from hydronephrotic kidneys devoid of macula densa structures was examined. 2. Basal flow rate through isolated kidneys was 13.5+/-1.0 ml min-1 g-1 at a renal artery pressure of 100 mmHg and corresponding renin secretory rates were 5.5+/-0.5 (ng angiotensin I (Ang I) h-1) min-1 g-1 (mean+/-S.E.M., n = 15). 3. Frusemide (10-100 muM) and bumetanide (5-50 muM) increased urine flow rates and stimulated urinary sodium excretion in a dose-dependent fashion from 13.0+/-2.5 mumol min-1 g-1 (n = 10) under control conditions to maximal values of 38.0+/-5.0 (n = 5) and 37.0+/-2.0 mumol min-1 g-1 (n = 5), respectively. Both drugs also induced concentration-dependent decreases of the renal vascular resistance. The vasorelaxant effects of frusemide and bumetanide were paralleled by an increase of renin secretion to a maximum of 21+/-4 (ng Ang I h-1) min-1 g-1 (n = 10). On a molar basis bumetanide was twice as potent as frusemide in stimulating renin secretion. 4. Lowering of the perfusion pressure from 100 to 40 mmHg resulted in a prompt increase of renin release yielding secretion rates of 92+/-10 (ng Ang I h-1) min-1 g-1 (n = 15). In the presence of frusemide (100 muM) and bumetanide (50 muM) renin secretion rates at 40 mmHg were 97+/-11 and 133+/-24 (ng Ang I h-1) min-1 g-1 (n = 6), respectively. Renin release stimulated by bumetanide was significantly reduced to 8.0+/-1.5 (ng Ang I h-1) min-1 g-1 (n = 5) by elevating the perfusion pressure from 100 to 140 mmHg. 5. Lowering the renal artery pressure from 100 to 40 mmHg in isolated perfused rat hydronephrotic kidneys devoid of tubular structures increased renin secretion rates from 4.5+/-1.0 to 22.5+/-2.5 (ng Ang I h-1) min-1 (n = 5). 6. In conclusion, our results suggest that the pressure-dependent renin secretion system does not require the macula densa signal. At normal pressure values (around 100 mmHg), the macula densa mechanism mediates approximately 20% of pressure-related inhibition of renin release. Moreover, renin secretion which is susceptible to the macula densa signal is at the same time under the direct and predominant control of the renal artery pressure.