Disparate effects of calcium channel blockers on pressure dependence of renin secretion and flow in the isolated perfused rat kidney.

Holger Scholz,Armin Kurtz

doi:10.1007/bf00374822

Abstract

Using the model of isolated perfused rat kidneys this study was performed to investigate whether or not voltage-operated calcium channels are essentially involved in the pressure control of renin secretion from the kidneys. At a perfusion pressure of 100 mm Hg (13.3 kPa) renin secretory rates were 4.2 +/- 0.7 (ng angiotensin I h-1) min-1 g-1. Stepwise reduction of renal perfusion pressure to 80, 60, and 40 mm Hg (10.6, 8.0, 5.3 kPa) resulted in an increase of renin release yielding a 30-fold stimulation at 40 mm Hg vs 100 mm Hg. Increasing the perfusion pressure above 100 mm Hg did not further significantly decrease renin secretion. The perfusate flow rate was also pressure-dependent. Flow rates increased linearly with pressure and reached a plateau at 100 mm Hg, which was maintained up to 160 mm Hg (21.3 kPa). The averaged flow rate at the plateau was 15.5 ml min-1 g-1. In the presence of the three different calcium antagonists nifedipine (5 microM), nitrendipine (3 microM) and verapamil (5 microM), myogenic autoregulation of flow was abolished as indicated by the rise of the pressure/flow curve between 40 and 160 mm Hg. At the same time, however, these calcium channel blockers did not alter the relationship between perfusion pressure and renin secretion. Moreover, the calcium channel agonist Bay K 8644 (5 microM) caused a strong and long-lasting vasoconstriction, without changing renin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Highlights

Since the original work by Goldblatt [10] it has been well established that the blood pressure is an essential control factor for the secretion of renin from the kidneys [7, 17, 20, 34, 38]
Since juxtaglomerular epitheloid (JG) cells are transformed vascular smooth muscle cells and since calcium is considered as an inhibitory signal for renin secretion it has been speculated that a similar mechanism involving the activation of voltageoperated calcium channels (VOCC) mediates the control of renin secretion by the pressure [9]
Pressure-dependent renin secretion from renal juxtaglomerular (JG) cells makes an important contribution to the homeostasis of systemic blood pressure [12]

Summary

Introduction

Since the original work by Goldblatt [10] it has been well established that the blood pressure is an essential control factor for the secretion of renin from the kidneys [7, 17, 20, 34, 38]. Tobian [37] proposed the existence of a renal "baroreceptor" that responds to stretching of the afferent arteriole This idea was further developed by Fray [8], who presented a mathematical stretch receptor model based on his studies of the perfused rat kidney. According to this model it has been suggested that the intraluminal pressure in the afferent arterioles has influence on the stretch of the smooth muscle cells in the media layer. Since JG cells are transformed vascular smooth muscle cells and since calcium is considered as an inhibitory signal for renin secretion (cf [14]) it has been speculated that a similar mechanism involving the activation of VOCC mediates the control of renin secretion by the pressure [9]. Evidence for a functional role of dihydropyridinesensitive calcium channels in the control ofrenin secretion from isolated rat kidneys is controversial [6, 13, 16, 24]

Methods

Results

Conclusion