Chloride channel blockers attenuate the inhibition of renin secretion by angiotensin II.
The aim of this study was to assess the relevance of chloride channels to the inhibitory effect of angiotensin II (ANGII) on renin secretion. We thus examined the effects of the chloride channels blockers IAA-94 and niflumic acid, the Na-K-Cl cotransport blocker bumetanide and substitution of isethionate for extracellular chloride on the action of ANGII on renin secretion from isolated perfused rat kidneys. Renin secretion prestimulated by isoproterenol (10 nmol/l) was almost completely blocked by ANGII with a concentration yielding a half-maximal response (EC50) of around 150 nmol/l. In the presence of IAA-94 and niflumic acid the EC50 for ANGII was shifted to about 400 nmol/l. In the presence of bumetanide and isethionate renin secretion responded more sensitively to ANGII and the EC50 for ANGII was below 100 nmol/l. On the assumption that the chloride equilibrium potential in renin-secreting cells is more positive than the membrane potential, our findings would suggest that the inhibitory effect of ANGII is enhanced when chloride entry is blocked and attenuated when chloride efflux is impaired. Activation of chloride channels therefore probably contributes to the inhibitory action of ANGII on renin secretion.
Nabel
C
C
Medizinische Klinik II, Universität Regensburg, Germany.
Schweda
F
F
Riegger
G A
GA
Krämer
B K
BK
Kurtz
A
A
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D002712:Chlorides / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology; D006016:Glycolates / Q000494:pharmacology; D007513:Isethionic Acid / Q000494:pharmacology; D008297:Male; D009544:Niflumic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters; D000092502:Renin Inhibitors
D000804:Angiotensin II; D002034:Bumetanide; D002352:Carrier Proteins; D018118:Chloride Channels; D002712:Chlorides; D004232:Diuretics; D006016:Glycolates; D007513:Isethionic Acid; D009544:Niflumic Acid; D012083:Renin; D028021:Sodium-Potassium-Chloride Symporters; D000092502:Renin Inhibitors; C015765:MK 473