E. Sehic et al., MECHANISM OF RESISTANCE TO ALPHA-ADRENERGIC RECEPTOR ANTAGONISTS OF RENAL NERVE STIMULATION-INDUCED VASOCONSTRICTION AT LOW-FREQUENCIES, Journal of cardiovascular pharmacology, 29(1), 1997, pp. 97-108
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.