MECHANISM OF RESISTANCE TO ALPHA-ADRENERGIC RECEPTOR ANTAGONISTS OF RENAL NERVE STIMULATION-INDUCED VASOCONSTRICTION AT LOW-FREQUENCIES

To determine why renal vasoconstriction elicited by periarterial nerve stimulation (RNS) at lower frequencies (<4 Hz) is resistant to alpha- adrenergic receptor blockade in the rat kidney, we reevaluated the eff ect of alpha-receptor antagonists on the vasoconstrictor response to n orepinephrine (NE) and to RNS and on the release of adrenergic transmi tter. The alpha-receptor antagonist prazosin (PZ) at 0.2 and 7 nM redu ced the vasoconstrictor response to NE, and 2.4 mu M PZ abolished it. PZ (0.2 or 7 nM) reduced RNS-induced vasoconstriction without altering the fractional tritium overflow. PZ (2.4 mu M) enhanced fractional tr itium overflow and reduced the vasoconstrictor response to RNS at 2-10 Hz, but not at 0.5 or 1 Hz. The effect of 0.2 nM PZ to reduce RNS-ind uced vasoconstriction was reversed by increasing the concentration to 2.4 mu M. Corynanthine (COR; 2.6 mu M), a preferential alpha-receptor blocker, or phenoxybenzamine (PBZ; 30 nM) abolished the vasoconstricto r response to NE but only partially reduced response to RNS and enhanc ed the fractional tritium overflow. Rauwolscine (RW; 2.5 nM), a prefer ential alpha(2)-receptor antagonist, did not alter the vasoconstrictor response to NE but potentiated RNS-induced vasoconstriction and fract ional tritium overflow. RW (7.7 mu M) inhibited NE-induced vasoconstri ction but potentiated the vasoconstrictor response to RNS and fraction al tritium overflow. PZ (7 nM) abolished the potentiation by RW and re duced the vasoconstrictor response to RNS. These data suggest that a c omponent of RNS-induced vasoconstriction in the rat kidney is attribut able to co-release of a nonadrenergic transmitter with NE. The diminis hed effect of alpha-receptor antagonists at higher concentrations (e.g ., PZ 2.4 mu M) to reduce RNS-induced vasoconstriction is caused by th eir prejunctional action to enhance co-release of the nonadrenergic tr ansmitter.