We examined the effects of cilnidipine, which is an L and N-type Ca2+ channel blocker, on adrenergically regulated renal functions in anesthetized dogs. Renal nerve stimulation (RNS) at high fre quency (3-7 Hz) decreased renal blood flow (RBF) without changes in systemic blood pressure. The RBF response was inhibited by intrarenal arterial (i.r.a.) infusion of cilnidipine at 0.1-0.3 ƒÊg/kg/min. Low frequency RNS (0.5-1 Hz) reduced absolute and fractional urinary sodium excretion. These responses were attenuated during i.r.a. infusion of cilnidipine at 0.3 ƒÊg/kg/min. An increase in norepinephrine secretion rate induced by low-frequency RNS was also attenuated during cilnidipine infusion. These results suggest that cilnidipine can suppress norepinephrine release from the renal nerve endings and thereby interfere with the neural control of renal functions.

Adrenal medullary chromaffin cells secrete catecholamines in response to nicotinic agonists (Douglas & Rubin, 1961;Wakade, 1981;Amy & Kirshner, 1982). Activation of the nicotinic receptors opens non-selective cation channels (Zhou & Neher, 1993) to depolarize the membrane of chromaffin cells (Douglas et al. 1967;Biales et al. 1976;Kilpatrick, 1984). This depolarization opens voltage-dependent Na¤ and Ca¥ channels, and the subsequent elevation of intracellular free Ca¥ is an essential step in the exocytotic secretion of adrenal catecholamines (Cheek et al. 1989;Kim & Westhead, 1989). Several types of voltage-dependent Ca¥ channels are present on adrenal chromaffin cells, but the role of each type in the catecholamine secretion process remains controversial. Cat chromaffin cells possess L_ and N-type voltage-dependent Ca¥ channels which each carry 50% of the Ca¥ current (Albillos et al. 1994), but the L-type Ca¥ channels dominate the exocytotic process (Lopez et al. 1994a). Bovine chromaffin cells possess not only L_ (Artalejo et al. 1991) and N-type voltage-dependent Ca¥ channels (Hans et al. 1990;Artalejo et al. 1992) but also P- (Mintz et al. 1992;Gand úa et al. 1994) and Q-type voltage-dependent Ca¥ channels (Lopez et al. 1994b), and the L_ and Q-type Ca¥ channels dominate the exocytotic process (Lomax et al. 1997). Rat chromaffin cells possess L_, N-, P-and Q-type voltage-dependent Ca¥ channels (Gand úa et al. 1995). Both L_ and N-type Ca¥ currents have been shown to be recruited during exocytosis from rat chromaffin cells (Kim et al. 1995). Thus not all of the voltage-dependent Ca¥ channels present in chromaffin cells may contribute to the secretion of catecholamines. Adrenal catecholamine secretion is also mediated by muscarinic receptors in various species (Douglas & Poisner, 1965;Harish et al. 1987;Nakazato et al. 1988;Kimura et al. 1992). Concerning the role of voltage-dependent Ca¥ channels in the muscarinic receptor-mediated secretion of catecholamines, observations obtained with L-type voltagedependent Ca¥ channel blockers in in vitro studies remain controversial. Verapamil, an L-type voltage-dependent Ca¥ channel blocker, does not affect muscarine-induced catecholamine secretion from perfused rat adrenal gland (Harish et al. 1987). In contrast, isradipine, another L_type voltage-dependent Ca¥ channel blocker, inhibits the methacholine-induced catecholamine secretion from cat chromaffin cells (Uceda et al. 1992). On the other hand, little is known about the involvement of N-type voltage-

1 We examined eects of g-aminobutyric acid (GABA) on vasoconstriction and noradrenaline (NA) release induced by electrical renal nerve stimulation (RNS) in the isolated pump-perfused rat kidney. 2 RNS (1 and 2 Hz for 2.5 min each, 0.5-ms duration, supramaximal voltage) increased renal perfusion pressure (PP) and renal NA eux. GABA (3, 10 and 100 mM) attenuated the RNSinduced increases in PP by 10 ± 40% (P50.01) and NA eux by 10 ± 30% (P50.01). GABA did not aect exogenous NA (40 and 60 nM)-induced increases in PP. 3 The selective GABA B agonist baclofen (3, 10 and 100 mM) also attenuated the RNS-induced increases in PP and NA eux, whereas the RNS-induced responses were relatively resistant to the selective GABA A agonist muscimol (3, 10 and 100 mM). 4 The selective GABA B antagonist 2-hydroxysaclofen (50 mM), but not the selective GABA A antagonist bicuculline (50 mM), abolished the inhibitory eects of GABA (10 mM) on the RNSinduced responses. 5 The selective a 2 -adrenoceptor antagonist rauwolscine (10 nM) enhanced the RNS-induced responses. GABA (3, 10 and 100 mM) potently attenuated the RNS-induced increases in PP by 40 ± 60% (P50.01) and NA eux by 20 ± 50% (P50.01) in the presence of rauwolscine. 6 Prazosin (10 and 30 nM) suppressed the RNS-induced increases in PP by about 70 ± 80%. Neither rauwolscine (10 nM) nor GABA (10 mM) suppressed the residual prazosin-resistant PP response. 7 These results suggest that GABA suppresses sympathetic neurotransmitter release via presynaptic GABA B receptors, and thereby attenuates adrenergically induced vasoconstriction in the rat kidney.

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