Supersensitivity to norepinephrine in chronically denervated kidneys: evidence for a postsynaptic effect.
Denervation supersensitivity in chronically denervated kidneys increases renal responsiveness to increased plasma levels of norepinephrine. To determine whether this effect is caused by presynaptic (i.e., loss of uptake) or postsynaptic changes, we studied the effect of continuous infusion of norepinephrine (330 ng/min, i.v.) and methoxamine (4 micrograms/min, i.v.), an alpha 1-adrenergic agonist that is not taken up by nerve terminals, on renal function of innervated and denervated kidneys. Ganglionic blockade was used to eliminate reflex adjustments in the innervated kidney and mean arterial pressure was maintained at preganglionic blockade levels by an infusion of arginine vasopressin. With renal perfusion pressure controlled there was a significantly greater decrease in renal blood flow (-67 +/- 9 vs. -33 +/- 8%), glomerular filtration rate (-60 +/- 9 vs. -7 +/- 20%), urine flow (-61 +/- 7 vs. -24 +/- 11%), sodium excretion (-51 +/- 15 vs. -32 +/- 21%), and fractional excretion of sodium (-50 +/- 9 vs. -25 +/- 15%) from the denervated kidneys compared with the innervated kidneys during the infusion of norepinephrine. During the infusion of methoxamine there was a significantly greater decrease from the denervated compared with the innervated kidneys in renal blood flow (-54 +/- 10 vs. -30 +/- 14%), glomerular filtration rate (-51 +/- 11 vs. -19 +/- 17%), urine flow (-55 +/- 10 vs. -39 +/- 10%), sodium excretion (-70 +/- 9 vs. -59 +/- 11%), and fractional excretion of sodium (-53 +/- 10 vs. -41 +/- 10%).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000494:pharmacology; D003714:Denervation; D005730:Ganglionic Blockers / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000294:innervation; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects; D013569:Synapses / Q000187:drug effects*
D005730:Ganglionic Blockers; D006584:Hexamethonium Compounds; D001127:Arginine Vasopressin; D008729:Methoxamine; D009638:Norepinephrine