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Supersensitivity to norepinephrine in chronically denervated kidneys: evidence for a postsynaptic effect
J Krayacich1, R L Kline, P F Mercer
1Department of Physiology, University of Western Ontario, London, Canada.
Canadian Journal of Physiology and Pharmacology
|November 1, 1987
Summary
Denervation supersensitivity makes kidneys more responsive to norepinephrine. This study shows that both norepinephrine and methoxamine cause greater renal function decline in denervated kidneys, indicating postsynaptic changes are responsible.
Area of Science:
- Nephrology
- Renal Physiology
- Adrenergic Pharmacology
Background:
- Chronically denervated kidneys exhibit supersensitivity to norepinephrine.
- This heightened responsiveness may stem from presynaptic (uptake) or postsynaptic alterations.
Purpose of the Study:
- To differentiate between presynaptic and postsynaptic mechanisms underlying denervation supersensitivity in the kidney.
- To investigate the impact of norepinephrine and methoxamine on renal function in innervated versus denervated kidneys.
Main Methods:
- Continuous intravenous infusion of norepinephrine and methoxamine (an alpha 1-adrenergic agonist) in innervated and denervated kidneys.
- Ganglionic blockade to prevent reflex adjustments and arginine vasopressin infusion to maintain mean arterial pressure.
- Controlled renal perfusion pressure to isolate drug effects on renal hemodynamics and function.
Main Results:
- Denervated kidneys showed significantly greater decreases in renal blood flow, glomerular filtration rate, urine flow, and sodium excretion compared to innervated kidneys during norepinephrine infusion.
- Similar, pronounced declines in renal function were observed in denervated kidneys versus innervated kidneys during methoxamine infusion.
- These findings suggest that the inability of nerve terminals to reuptake norepinephrine does not account for the enhanced renal response.
Conclusions:
- Postsynaptic changes, rather than presynaptic alterations like reduced uptake, are the primary drivers of denervation supersensitivity in the kidney.
- The kidney's response to alpha 1-adrenergic stimulation is significantly amplified following chronic denervation.