A biphasic effect of noradrenaline on renin release from rat juxtaglomerular cells in vitro is mediated by alpha 1- and beta-adrenoceptors.
The direct effect of noradrenaline on renin release from juxtaglomerular (JG) cells in vitro were investigated in a dynamic superfusion system of dispersed rat renal cortical cells. At low concentrations (1-100 nmol/l), noradrenaline stimulated renin release in a dose-dependent manner, while at higher concentrations (0.1-1 mmol/l) it inhibited renin release. The stimulatory effect of 0.1 mumol noradrenaline/l was completely blocked by a beta-adrenoceptor antagonist, propranolol (0.1 mumol/l). When applied at concentrations of 1 mumol/l or 10 mumol/l, noradrenaline had no consistent effect on renin release, although 10 mumol noradrenaline/l had an inhibitory effect in the presence of propranolol (0.1 mumol/l). The inhibitory effect of noradrenaline (0.1 mmol/l) was converted to a stimulatory effect by the addition of an alpha 1-adrenoceptor antagonist (bunazosin, 1 mumol/l), but was not altered by the addition of an alpha 2-adrenoceptor antagonist (yohimbine, 1 mumol/l). These results indicate that low concentrations of noradrenaline directly stimulate renin release from JG cells by the activation of beta-adrenoceptors, while high concentrations of noradrenaline inhibit renin release by the activation of alpha 1-adrenoceptors. Accordingly, a dynamic balance may exist between beta-adrenergic stimulation and alpha 1-adrenergic depression of renin release.
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
M
M
Takagi
K
K
Atarashi
H
H
Matsuoka
T
T
Sugimoto
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D010477:Perfusion; D011433:Propranolol / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D012083:Renin / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; D015016:Yohimbine; C018176:bunazosin; D011433:Propranolol; D012083:Renin; D009638:Norepinephrine