European Journal of Pharmacology, 57 (1979) 107--113
107
© Elsevier/North-Holland Biomedical Press
STUDIES ON THE CENTRAL PRESSOR ACTIVITY OF DIBUTYRYL CYCLIC AMP H. STEVE WHITE, PAUL S. DRIVER and GARY E. ISOM
Department of Pharmacology, Idaho State University, Pocatello, Idaho 83209, U.S.A. Received 7 January 1979, revised MS received 14 March 1979, accepted 24 April 1979
H.S. WHITE, P.S. DRIVER and G.E. ISOM, Studies on the central pressor activity of dibutyryl cyclic AMP, European J. Pharmacol. 57 (1979) 1 0 7 - 1 1 3 . The effects of the central administration (i.c.v.) of dibutyryl cyclic AMP (DBcAMP) on arterial blood pressure and heart rate were studied in the rat. The cyclic nucleotide produced a dose-dependent rise in blood pressure and an accompanying tachycardia. Maximal pressor effect of a single dose of DBcAMP (350 pg) was observed 25 rain post injection and the duration of the response was 60 rain. Chemical degeneration of central catecholaminergic neurons with 6-hydroxydopamine treatment abolished the pressor response to DBcAMP. Partial chemical degeneration of central serotonin pathways with 5,6-dihydroxytryptamine did not significantly alter the effect. The pressor activity of the cyclic nucleotide was attenuated by central administration of phentolamine. Spinal cord section at the C6-C7 level or peripheral chemical degeneration of catecholaminergic neurons combined with bilateral adrenalectomy abolished the pressor response to DBcAMP. It was concluded that the pressor response to i.c.v, administration of DBcAMP is mediated by central catecholaminergic pathways and is the result of an increase in efferent sympathetic outflow and release of catecholamines from the adrenal medulla. Central blood pressure control Arterial blood pressure
Dibutyryl cyclic AMP 5,6-Dihydroxytryptamine
1. Introduction
Cyclic AMP has been proposed to be an intracellular second messenger which mediates the action of several neurotransmitters in the CNS (Bloom, 1975). Activation of central adrenoreceptors increases cAMP levels in a number of brain structures such as the cerebral cortex and hypothalamus (Palmer et al., 1973; Skolnick and Daly, 1975) and the rise in cAMP levels has been postulated to initiate a series of intracellular events which increases excitability of the neuron (Daly, 1975). However, the relationship between brain cAMP levels and specific physiological functions has not been established (see Drummond and Ma, 1974, for review). Recently, Walland (1975, 1977) proposed that cAMP participates in the central regulation of blood pressure and the activity of cardiovascular centers is determined by their
6-Hydroxydopamine
content of cAMP. Furthermore, Delbarre et al. (1977) observed that manipulation of central cAMP levels influences peripheral cardiovascular functions. It is widely accepted that the central nervous system plays a critical role in the regulation of blood pressure (see Reis and Doba, 1974 for review) and a number of central sites such as the nucleus posterior of the hypothalamus (Przuntek et al., 1971), locus coeruleus (BjSrklund, 1977) and the nucleus tractus solitarii influence peripheral cardiovascular function via catecholaminergic mechanisms (see Chalmers, 1975 for review). In turn, cAMP may function as a second messenger in these catecholaminergic systems and changes in intraneuronal cAMP levels could produce marked alterations in arterial blood pressure. The present study was initiated in order to study in more detail the effects of central injections of N~,O:'
107
© Elsevier/North-Holland Biomedical Press
STUDIES ON THE CENTRAL PRESSOR ACTIVITY OF DIBUTYRYL CYCLIC AMP H. STEVE WHITE, PAUL S. DRIVER and GARY E. ISOM
Department of Pharmacology, Idaho State University, Pocatello, Idaho 83209, U.S.A. Received 7 January 1979, revised MS received 14 March 1979, accepted 24 April 1979
H.S. WHITE, P.S. DRIVER and G.E. ISOM, Studies on the central pressor activity of dibutyryl cyclic AMP, European J. Pharmacol. 57 (1979) 1 0 7 - 1 1 3 . The effects of the central administration (i.c.v.) of dibutyryl cyclic AMP (DBcAMP) on arterial blood pressure and heart rate were studied in the rat. The cyclic nucleotide produced a dose-dependent rise in blood pressure and an accompanying tachycardia. Maximal pressor effect of a single dose of DBcAMP (350 pg) was observed 25 rain post injection and the duration of the response was 60 rain. Chemical degeneration of central catecholaminergic neurons with 6-hydroxydopamine treatment abolished the pressor response to DBcAMP. Partial chemical degeneration of central serotonin pathways with 5,6-dihydroxytryptamine did not significantly alter the effect. The pressor activity of the cyclic nucleotide was attenuated by central administration of phentolamine. Spinal cord section at the C6-C7 level or peripheral chemical degeneration of catecholaminergic neurons combined with bilateral adrenalectomy abolished the pressor response to DBcAMP. It was concluded that the pressor response to i.c.v, administration of DBcAMP is mediated by central catecholaminergic pathways and is the result of an increase in efferent sympathetic outflow and release of catecholamines from the adrenal medulla. Central blood pressure control Arterial blood pressure
Dibutyryl cyclic AMP 5,6-Dihydroxytryptamine
1. Introduction
Cyclic AMP has been proposed to be an intracellular second messenger which mediates the action of several neurotransmitters in the CNS (Bloom, 1975). Activation of central adrenoreceptors increases cAMP levels in a number of brain structures such as the cerebral cortex and hypothalamus (Palmer et al., 1973; Skolnick and Daly, 1975) and the rise in cAMP levels has been postulated to initiate a series of intracellular events which increases excitability of the neuron (Daly, 1975). However, the relationship between brain cAMP levels and specific physiological functions has not been established (see Drummond and Ma, 1974, for review). Recently, Walland (1975, 1977) proposed that cAMP participates in the central regulation of blood pressure and the activity of cardiovascular centers is determined by their
6-Hydroxydopamine
content of cAMP. Furthermore, Delbarre et al. (1977) observed that manipulation of central cAMP levels influences peripheral cardiovascular functions. It is widely accepted that the central nervous system plays a critical role in the regulation of blood pressure (see Reis and Doba, 1974 for review) and a number of central sites such as the nucleus posterior of the hypothalamus (Przuntek et al., 1971), locus coeruleus (BjSrklund, 1977) and the nucleus tractus solitarii influence peripheral cardiovascular function via catecholaminergic mechanisms (see Chalmers, 1975 for review). In turn, cAMP may function as a second messenger in these catecholaminergic systems and changes in intraneuronal cAMP levels could produce marked alterations in arterial blood pressure. The present study was initiated in order to study in more detail the effects of central injections of N~,O:'
