Effect of norepinephrine on renin release and the cyclic AMP content of rat kidney slices: modification by sodium deficiency and alpha-adrenergic blockade.
The effect of L-norepinephrine (NE) on renin release by slices of kidney cortex from sodium-replete and sodium-deficient rats was studied in vitro. The rate of renin release by slices from sodium-deficient rats in the absence of added NE increased in proportion to the length of dietary sodium restriction and was significantly greater at all times than release by slices from sodium-replete animals. NE added to slices from the sodium-replete animals in concentrations ranging from 2 X 10(-9) to 2 X 10(-4)M caused a significant renin release only at a concentration of 2 X 10(-7)M. In contrast, the rate of renin release by slices from the sodium-deficient rats increased in a dose-related fashion when the NE concentration ranged from 2 X 10(-12) to 2 X 10(-7)M. NE in a concentration of 2 X 10(-5) had a lesser stimulatory effect, and 2 X 10(-4)M caused a significant inhibition of renin release. This inhibition was converted to stimulation by addition of the alpha-adrenergic blocking drug phentolamine. Phentolamine by itself was ineffective. The increases and decreases in renin release produced by NE were, in general, accompanied by increases and decreases in the cyclic AMP content of the slices. The changes in renin release were linear for 60 min, but the changes in cyclic AMP content were greater at 5 and 20 min than at 60 min. A dose-response relationship between the changes in renin release and cyclic AMP content was not observed. These data indicate that sodium deprivation enhances the sensitivity of the renin-secreting cells to catecholamine stimulation, and are consistent with the hypothesis that the increase in renin secretion produced by NE is mediated via cyclic AMP. The data also indicated that in high concentrations, NE exerts an inhibitory effect on renin release, and that this effect is mediated via stimulation of alpha-adrenergic receptors.
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology*; D051381:Rats; D012083:Renin / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology*
D012964:Sodium; D000242:Cyclic AMP; D012083:Renin; D009638:Norepinephrine; D010646:Phentolamine