APPARENT VASCULAR TO CARDIAC SYMPATHOLYTIC SELECTIVITY OF OMEGA-CONOTOXIN GVIA IN THE PITHED RAT

被引:24
作者
PRUNEAU, D
ANGUS, JA
机构
[1] Baker Medical Research Institute, Prahran, Vic., Commercial Road
关键词
Sympathetic nerves; Tachycardia; Vasoconstriction; ω-Conotoxin;
D O I
10.1016/0014-2999(90)90673-T
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The effects of ω-conotoxin GVIA (ω-CTX), a blocker of N-type voltage-operated calcium channels (VOCCs), were investigated in the pithed rat. ω-CTX (1.6 and 3.2 μg/kg i.v.) did not alter resting diastolic pressure or heart rate nor the pressor and chronotropic responses to noradrenaline injections (0.1-10 μg/kg). In contrast, the pressor responses to electrical stimulation of the whole spinal cord (0.2-6.4 Hz) were dose dependently reduced by ω-CTX whereas the concomitant tachycardia was less affected. When selective stimulation of the cardiac sympathetic outflow was applied, the resulting chronotropic response was more sensitive to ω-CTX. This result is discussed in the light of the possible interference of adrenal catecholamine release during whole spinal cord stimulation which is not sensitive to ω-CTX. These results provide in vivo evidence that ω-CTX is able to reduce sympathetic neurotransmission to the vasculature and the heart, presumably by blocking N-type VOCCs on pre- and post-ganglionic nerve terminals. © 1990.
引用
收藏
页码:127 / 133
页数:7
相关论文
共 21 条
[1]  
ARMITAGE P, 1971, STATISTICAL METHODS, P253
[2]   THE EFFECT OF BILATERAL ADRENAL DEMEDULLATION ON VASCULAR REACTIVITY AND BLOOD-PRESSURE IN SPONTANEOUSLY HYPERTENSIVE RATS [J].
BORKOWSKI, KR ;
QUINN, P .
BRITISH JOURNAL OF PHARMACOLOGY, 1983, 80 (03) :429-437
[3]   INHIBITION OF TRANSMITTER RELEASE FROM SYMPATHETIC-NERVE ENDINGS BY OMEGA-CONOTOXIN [J].
BROCK, JA ;
CUNNANE, TC ;
EVANS, RJ ;
ZIOGAS, J .
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 1989, 16 (04) :333-339
[4]   HEART RATE AS A DETERMINANT OF CARDIAC OUTPUT IN DOGS WITH ARTERIOVENOUS FISTULA [J].
COWLEY, AW ;
GUYTON, AC .
AMERICAN JOURNAL OF CARDIOLOGY, 1971, 28 (03) :321-&
[5]   DIFFERENTIAL EFFECT OF OMEGA-CONOTOXIN ON RELEASE OF THE ADRENERGIC TRANSMITTER AND THE VASOCONSTRICTOR RESPONSE TO NORADRENALINE IN THE RAT ISOLATED KIDNEY [J].
ELDIN, MMM ;
MALIK, KU .
BRITISH JOURNAL OF PHARMACOLOGY, 1988, 94 (02) :355-362
[6]   A METHOD OF STIMULATING DIFFERENT SEGMENTS OF AUTONOMIC OUTFLOW FROM SPINAL COLUMN TO VARIOUS ORGANS IN PITHED CAT AND RAT [J].
GILLESPIE, JS ;
MACLAREN, A ;
POLLOCK, D .
BRITISH JOURNAL OF PHARMACOLOGY, 1970, 40 (02) :257-+
[7]   DOMINANT ROLE OF N-TYPE CA-2+ CHANNELS IN EVOKED RELEASE OF NOREPINEPHRINE FROM SYMPATHETIC NEURONS [J].
HIRNING, LD ;
FOX, AP ;
MCCLESKEY, EW ;
OLIVERA, BM ;
THAYER, SA ;
MILLER, RJ ;
TSIEN, RW .
SCIENCE, 1988, 239 (4835) :57-61
[8]   CHARACTERIZATION OF THE EFFECTS OF OMEGA-CONOTOXIN GVIA ON THE RESPONSES OF VOLTAGE-SENSITIVE CALCIUM CHANNELS [J].
KEITH, RA ;
MANGANO, TJ ;
PACHECO, MA ;
SALAMA, AI .
JOURNAL OF AUTONOMIC PHARMACOLOGY, 1989, 9 (04) :243-252
[9]   A VENOM PEPTIDE WITH A NOVEL PRESYNAPTIC BLOCKING ACTION [J].
KERR, LM ;
YOSHIKAMI, D .
NATURE, 1984, 308 (5956) :282-284
[10]   THE EFFECT OF OMEGA CONOTOXIN GVIA, A PEPTIDE MODULATOR OF THE N-TYPE VOLTAGE SENSITIVE CALCIUM CHANNELS, ON MOTOR-RESPONSES PRODUCED BY ACTIVATION OF EFFERENT AND SENSORY NERVES IN MAMMALIAN SMOOTH-MUSCLE [J].
MAGGI, CA ;
PATACCHINI, R ;
SANTICIOLI, P ;
LIPPE, IT ;
GIULIANI, S ;
GEPPETTI, P ;
DELBIANCO, E ;
SELLERI, S ;
MELI, A .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1988, 338 (02) :107-113