Effect of chlorpromazine on sympathetic neuroeffector transmission in the rabbit isolated pulmonary artery and aorta

Abstract

The effects of chlorpromazine on sympathetic neuroeffector transmission have been studied in the rabbit isolated pulmonary artery and aorta. Chlorpromazine (10−8‐10−5 m), prazosin (10−9‐10−7 m) and phentolamine (3 × 10−8‐3 × 10−5 m) decreased the contractions of pulmonary artery evoked by electrical field stimulation (150 pulses; 3 Hz). The rank order of inhibitory potency (ID50) was prazosin > chlorpromazine > phentolamine. Rauwolscine (3 × 10−9 m‐4 × 10−6 m) enhanced the neurogenic response by up to 201%. However, higher concentrations (6 × 10−6‐3 × 10−5 m) reduced the contractions evoked by transmural stimulation. The inhibitory effect of prazosin (10−6 m) was reversible, while that of chlorpromazine (10−8 m) was not. Chlorpromazine (10−8‐10−4 m), desmethylimipramine (3 × 10−9‐10−5 m), cocaine (10−7‐3 × 10−4 m) and phentolamine (10−5‐3 × 10−4 m) reduced the accumulation of [3H]‐noradrenaline ([3H]‐NA, 10−8 m) by aorta. The rank order of inhibitory potency (ID50) was: desmethylimipramine > chlorpromazine > cocaine > phentolamine. Prazosin (10−7‐10−5 m) and rauwolscine (10−8‐10−4 m) did not reduce [3H]‐NA accumulation. Chlorpromazine (10−8‐10−6 m) and prazosin (3 × 10−9‐10−7 m) antagonized the contractions of aorta evoked by exogenous noradrenaline (10−9‐3 × 10−4 m) and phenylephrine (10−9‐3 × 10−3 m). The pA2 values for chlorpromazine on the α1‐adrenoceptors were 8.24 (noradrenaline) and 8.27 (phenylephrine). The corresponding values for prazosin were 8.64 and 8.57, respectively. It is concluded that chlorpromazine and prazosin are potent inhibitors of postsynaptic α1‐ adrenoceptors. Chlorpromazine and phentolamine, unlike prazosin and rauwolscine, are also inhibitors of Uptake.

Regional variation in electrically‐evoked contractions of rabbit isolated pulmonary artery

“…In the extrapulmonary region, using a brief pulse width (0.1 ms) monphasic contractions were evoked that were sympathetic in origin, confirming previous reports (i.e. Nedergaard & Abrahamsen, 1988). However, the contraction of the intrapulmonary region elicited by similar stimulation parameters was strikingly different consisting of an initial fast phase followed by a slow, long‐lasting second component.…”

“…In the extrapulmonary region, using a brief pulse width (0.1 ms) monphasic contractions were evoked that were sympathetic in origin, con®rming previous reports (i.e. Nedergaard & Abrahamsen, 1988). However, the contraction Figure 6 Calcium imaging.…”

“…It is well known that sympathetic nerve stimulation elicits noradrenaline release, which by action at α 1 ‐adrenoceptors, produced a prazosin‐sensitive contraction of the extrapulmonary artery (Nedergaard & Abrahamsen, 1988; MacLean et al ., 1993a). However, in the present study, the slow contraction of the intrapulmonary artery was largely unaffected by α‐adrenoceptor antagonists.…”

Effect of Dopexamine Hydrochloride on Contractions of Rabbit Isolated Aorta Evoked by Various Agonists

“…1 and 3). The PA,-values (table 1 and 2) for dopexamine (range: 6.60-7.06) indicate that dopexamine is a weaker a,-adrenoceptor antagonist than prazosin (8,48,6) in this tissue using the same agonists (Nedergaard & Abrahamsen 1988). The possibility that the antagonism was in any way due to inhibition of a,-adrenoceptors can be ruled out since rabbit aorta does not contain this subtype of postsynaptic adrenoceptors (Docherty et al 1981).…”

Frequency‐Dependence of 3H‐Noradrenaline Release from Rabbit Pulmonary Artery: Effect of α‐Adrenoceptor Antagonists and Inhibitors of Transmitter Inactivation

“…Chlorpromazine is a potent inhibitor of neuronal uptake of noradrenaline (Nedergaard & Abrahamsen 1988). Chlorpromazine is a potent inhibitor of neuronal uptake of noradrenaline (Nedergaard & Abrahamsen 1988).…”