Endothelium-derived NO stimulates pressure-dependent renin release in conscious dogs

Abstract

The effect of blocking the formation of endothelium-derived relaxing factor/nitric oxide (EDNO) on pressure-dependent renin release (RR) was studied in six conscious foxhounds with chronically implanted catheters in the abdominal aorta and the renal vein. Renal blood flow (RBF) was measured with an ultrasonic transit-time flowmeter. RR was determined by multiplying the renal venous-arterial plasma renin activity difference with renal plasma flow. Renal artery pressure (RAP) was reduced in steps by a pneumatic occluder placed around the suprarenal abdominal aorta. A dose of 1,000 mg NG-nitro-L-arginine methyl ester (L-NAME) was given as a bolus to inhibit EDNO formation. In response to L-NAME, RAP increased (98 +/- 3 vs. 128 +/- 3 mmHg; P < 0.05), heart rate decreased (88 +/- 7 vs. 51 +/- 5 beats/min; P < 0.05), RBF decreased (280 +/- 19 vs. 185 +/- 24 ml/min; P < 0.05), and RR decreased (62 +/- 11 vs. 28 +/- 7 U; P < 0.05), whereas glomerular filtration rate changed little (38 +/- 3 vs. 35 +/- 4 ml/min; not significant). Below roughly 90 mmHg, RR was considerably attenuated by L-NAME as RAP was reduced in steps. At the lowest RAP (50 mmHg) RR was 1,946 +/- 406 U during control vs. 697 +/- 179 U after L-NAME (P < 0.05). Thus L-NAME inhibited pressure-dependent RR. This was especially pronounced in the low-pressure range.

Role of calcium ions in the pressure control of renin secretion from the kidneys

“…1). To test for pressure dependence of renin release the perfusion pressure was adjusted stepwise to 140, 100, 80 and 40 mmHg (19,13,11,5 kPa). As shown in Fig.…”

“…Accumulating evidence suggests that endotheliumderived relaxing factor/nitric oxide (EDRF/NO) [18] is a potent stimulus for renin release in vivo [17,19] and in vitro [6,15,21,23]. In particular, EDRF/NO has been reported to account for the substantial part of renin secretion which is stimulated by low renal artery pressure [21].…”

“…More direct experimental approaches such as patch-clamp studies [10] and experiments on isolated glomeruli [12] failed to support a role of voltage-operated Ca 2+ channels in the pressure-mediated control of renin secretion [20]. In addition, recent observations have demonstrated that endothelium-derived relaxing factor/nitric oxide (EDRF/NO) is required for the normal relationship between renal perfusion pressure and renin release [19,21]. Since EDRF formation is strongly calcium-dependent [13] any manoeuvre modulating transmernbrane calcium entry into endothelial cells would affect EDRF release.…”

“…In this study we examined the role of calcium ions in the control of renin release by the renal artery pressure. For this purpose renin secretion rates (RSR) were measured in isolated rat kidneys perfused at pressures of 140, 100, 80 and 40 mmHg [19,13,11, 5 kPa) with media containing either 1.5 retool/1 ("normal") or zero calcium concentrations (calcium-free perfusate with 0.5 mmol/1 EGTA). At normal calcium the RSR was inversely related to the renal artery pressure, whereas calcium withdrawal resulted in an almost linear and proportional relationship between RSR and perfusion pressure.…”

Endothelium derived relaxing factor is involved in the pressure control of renin gene expression in the kidney

“…There is accumulating evidence that endothelium derived relaxing factor (EDRF), which is considered to be nitric oxide (NO), is a potent modulator of renin secreCorrespondence to: K. Schricker tion from the kidneys [1,8,11,15,16,18,23,24,27], A potential physiological role of EDRF/NO (or EDNO) in the control of renin secretion is, moreover, suggested by the high level expression of NO-synthase in renal macula densa cells [14,26,28], which are directly adjacent to juxtaglomerular (JG) cells which produce, store and release renin in a regulated fashion [9]. The precise effect of EDNO on renin secretion, however, is still a matter of controversy.…”