Age-related changes in vascular sympathetic neurotransmission in the rat kidney.
The objective of this study was to determine the effects of aging on sympathetic neurotransmission in an important vascular resistance bed, the kidney. The experimental model utilized was the isolated perfused kidney from male Fischer 344 rats, 6, 12 and 24 months of age. Stimulus-induced (supramaximal V, 30 pulses, 1 msec) overflow of endogenous norepinephrine was examined over a wide range of frequencies (0.25-12 Hz) under three conditions: 1) control; 2) after inhibition of neuronal and extraneuronal uptake; and 3) after blockade of alpha adrenoceptors. Absolute overflow of norepinephrine was significantly greater in the 24-month group compared to the 6- and 12-month groups. Because renal catecholamine content was not significantly different between the three groups, fractional overflow also was significantly greater in the 24-month group. Despite the increase in overflow in the 24-month group, control vasoconstrictor responses to nerve stimulation were not significantly different between the three groups. Inhibition of neuronal and extraneuronal uptake did not significantly alter the relationship between fractional overflows in the three groups. In the presence of alpha adrenoceptor blockade, utilized to eliminate the influence of inhibitory prejunctional alpha adrenoceptors, fractional overflow of norepinephrine was increased in each group compared to control. However, after alpha adrenoceptor blockade, fractional overflow was not significantly different between the three age groups. In conclusion, aging results in a decrease in prejunctional alpha adrenoceptor influence and increase in norepinephrine release from renal sympathetic nerves, but not alterations in vascular response to sympathetic nerve activation.
Eikenburg
D C
DC
Department of Pharmacology, College of Pharmacy, University of Houston, Texas.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D004558:Electric Stimulation; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014655:Vascular Resistance / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D003042:Cocaine; D003345:Corticosterone; D009638:Norepinephrine