Summary
The electrical stimulation of the paraventricular nucleus (PVN) of the hypothalamus in anaesthetized rabbits elicited important cardiovascular responses which were mainly characterized by increases in arterial pressure, dP/dtmax, and of the indexes of myocardial oxygen consumption, rate-pressure product (from 34±2 to 40±2 mmHg · bpm · 10−3) and triple product (from 102±12 to 162±19 mmHg2 · s−1 · bpm · 10−6). The hemodynamic alterations induced by PVN stimulation were similar to those observed during physical effort and stressful situations. Intracerebroventricular (0.1, 0.3 and 1 μg · kg−1) or intravenous administration (1, 3 and 10 mg · kg−1) of baclofen, a selective GABAB receptor agonist, induced a dose-related decrease in the peak values of dP/dtmax and of the indexes of myocardial oxygen consumption (rate-pressure and triple products) during the electrical PVN stimulation. After 1 μg · kg−1 baclofen (i.cv.), the peak value of the triple product during PVN stimulation was 101±21 as compared to 149±15 before treatment. At the 10 mg · kg−1 dose (iv.), the triple product during stimulation only reached 90±20 vs. 150±20 before treatment. These results suggested that a type B GABAergic transmission system is involved in the modulation of central control of the cardiac function. Drugs modulating this system could therefore be designed to blunt the myocardial oxygen demand increases.
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References
Antonaccio MJ, Taylor DG (1977) Involvement of central GABA receptors in the regulation of blood pressure and heart rate of anaesthetized cats. Eur J Pharmacol 46:283–287
Antonaccio MJ, Kervin L, Taylor DG (1978) Reductions in blood pressure, heart rate and renal sympathetic nerve discharge in cats after the central injection of muscimol, a GABA agonist. Neuropharmacology 17:783–791
Azevedo AD, Hilton SM, Timms RJ (1980) The defence reaction elicited by midbrain and hypothalamic stimulation in the rabbit. J Physiol London 301:56P–57P
Baller D, Bretschneider HJ, Hellige G (1979) Validity of myocardial oxygen consumption parameters. Clin Cardiol 2:317–327
Bauer RM, Vela MB, Simon T, Waldrop TG (1988) A GABAergic mechanism in the posterior hypothalamus modulates baroreflex bradycardia. Brain Res Bull 20:633–641
Bhargava KP, Battacharya SS, Srimal RC (1964) Central cardiovascular actions of γ-aminobutyric acid. Br J Pharmacol 23:383–390
Bonham AC, Gutterman DD, Arthur JM, Marcus ML, Gebhart GF, Brody MJ (1987) Electrical stimulation in perifornical lateral hypothalamus decreases coronary blood flow in cats. Am J Physiol 252:H474-H484
Bousquet P, Feldman J, Bloch R, Schwartz J (1981) The central hypotensive action of baclofen in the anaesthetized cat. Eur J Pharmacol 76:193–201
Bousquet P, Feldman J, Bloch R, Schwartz J (1984) Pharmacological analyses of the central cardiovascular effects of four GABA analogues. Naunyn-Schmiedeberg's Arch Pharmacol 319:168–171
Bousquet P, Feldman J, Schwartz J (1985) The medullary cardiovascular effects of imidazolines and some GABA analogues: a review. J Auton Nerv Sys 14:263–270
Bowery N (1989) GABAB receptors and their significance in mammalian pharmacology. Trends Pharmacol Sci 10:401–407
Cohn PF (1992) Mechanisms of myocardial ischemia. Am J Cardiol 70:14G–18G
Ciriello J, Calaresu FR (1980) Role of supraventricular and supraoptic nuclei in central cardiovascular regulation in the cat. Am J Physiol 239:R137-R142
Elekes I, Pathy A, Lang T, Palkovits M (1986) Concentrations of GABA and glycine in discrete brain nuclei: Stress-induced changes in the levels of inhibitory aminoacids. Neuropharmacology 25:703–709
Elliott KAC, Hobbiger F (1959) Gamma-amino-butyric acid: Circulatory and respiratory effects in different species: re-investigation of the antistrychnine effect in mice. J Physiol (Lond) 146:70–84
Fukuda T, Kudo Y, Ono H (1977) Effects of (β-(p-chlorophenyl)-GABA)-baclofen on spinal synaptic activity. Eur J Pharmacol 44:17–24
Goodchild AK, Dampney RAL, Bandler R (1982) A method for evoking physiological responses by stimulation of cell bodies, but not axons of passage, within localized regions of the central nervous system. J Neurosci Methods 6:351–363
Head GA, Badoer E, Korner PI (1987) Cardiovascular role of A1 catecholaminergic neurons in the rabbit effect of chronic lesions on responses to methyldopa, clonidine and 6-OHDA induced transmitter release. Brain Res 412:18–28
Kaplan JA (1983) Protection of the ischemic myocardium. In: Kaplan JA (ed) Cardiac anesthesia, Vol 2, Cardiovascular pharmacology. Grune and Stratton, New York, pp 145–149
Lown B, Verrier R, Rabinowitz S (1977) Neural and psychologic mechanisms and the problem of sudden cardiac death. Am J Cardiol 39:890–902
Martin DS, Segura T, Haywood JR (1991) Cardiovascular responses to bicuculline in the paraventricular nucleus of the rat. Hypertension 18:48–55
McCulloch RM, Johnston GAR, Game CJA, Curtis DR (1974) The differential sensitivity of spinal interneurones and renshaw cells to kainate and N-methyl-D-aspartate. Exp Brain Res 21:515–518
Philippu A, Przuntek H, Roentsberg W (1973) Superfusion of the hypothalamus with gamma-aminobutyric acid. Effect on the release of noradrenaline and blood pressure. Naunyn-Schmiedeberg's Arch Pharmacol 308:137–142
Reich P, Da Silva RA, Lown B, Murawski J (1981) Acute psychiological disturbances preceding life-threatening ventricular arrhythmias. JAMA 246:233–235
Robinson BF (1967) Relation of heart rate and systolic blood pressure to onset of pain in angina pectoris. Circulation 35:1073–1083
Sample RHB, Di Micco JA (1987) Localization of sites in periventricular forebrain mediating cardiovascular effects of γ-aminobutyric acid agonists and antagonists in anaesthetized cats. J Pharmacol Exp Ther 240:498–507
Sawchenco PE, Swanson LW (1982) The organization of noradrenergic pathways from the brainstem to paraventricular and supraoptic nuclei in the rat. Brain Res Rev 4:275–325
Sawyer CH, Everett JW, Green JD (1954) The rabbit diencephalon in stereotaxic coordinates. J Comp Neurol 101:801–824
Schmidt B, Di Micco JA (1984) Blockade of GABA receptors in the periventricular forebrain of anaesthetized cats: Effects on heart rate, arterial pressure and hindlimb vascular resistance. Brain Res 301:111–119
Segura T, Hasser EM, Shade RE, Haywood JR (1989) Evidence for a forebrain GABAergic system capable of inhibiting baroreceptor-mediated vasopressin release. Brain Res 499:53–62
Specchia G, De Servi S, Falcone C, Gavazzi A, Angoli L, Bramucci E, Ardissino D, Mussini A (1984) Mental arithmetic stress testing in patients with coronary artery disease. Am Heart J 108:56–63
Swanson LW, Sawchenco PE (1983) Hypothalamic integration: organization of the paraventricular and supraoptic nuclei. Ann Rev Neurosci 6:269–324
Waldrop TG, Bauer RM, Iwamoto GA (1988) Microinjection of GABA antagonists into the posterior hypothalamus elicits locomotor movements and a cardiorespiratory activation. Brain Res 444:84–94
Williford DJ, Dimicco JA, Gillis RA (1980a) Evidence for the presence of a tonically active forebrain GABA system influencing central sympathetic outflow in the cat. Neuropharmacology 19:245–250
Williford DJ, Hamilton BL, Dias Souza J, Williams TP, Dimicco JA, Gillis RA (1980b) Central nervous system mechanisms involving GABA influence arterial pressure and heart rate. Circ Res 47:80–88
Yamada KA, Norman WP, Hamosh P, Gillis RA (1978) Medullary ventral surface GABA receptors affect respiratory and cardiovascular functions. Brain Res 248:71–78
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Tibirica, E., Monassier, L., Feldman, J. et al. Baclofen prevents the increase of myocardial oxygen demand indexes evoked by the hypothalamic stimulation in rabbits. Naunyn-Schmiedeberg's Arch Pharmacol 348, 164–171 (1993). https://doi.org/10.1007/BF00164794
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DOI: https://doi.org/10.1007/BF00164794