The role of capsaicin-sensitive neuropeptides and the intrinsic cardiac ganglia on cardiodynamics and atrial natriuretic peptide (ANP) release

Power, Roberta Patricia (1993) The role of capsaicin-sensitive neuropeptides and the intrinsic cardiac ganglia on cardiodynamics and atrial natriuretic peptide (ANP) release. Masters thesis, Memorial University of Newfoundland.

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Abstract

Atrial natriuretic peptide (ANP) is a circulating hormone, released from the heart, whose natriuretic and diuretic actions play an important role in cardiovascular homeostasis. It is stored as a prohormone in cardiac myocytes and converted to a circulating form upon release from the myocytes. Numerous factors have been shown to modulate ANP release, however the principal stimulus for release is believed to be stretch of the atrial wall. -- Recently it has been demonstrated that the capsaicin-sensitive peptidergic innervation of the rat heart, namely the substance P (SP) and calcitonin gene-related peptide (CGRP) fibers, is a component modulating the release of immunoreactiveANP (irANP). This research project initially investigated the role of the intrinsic cardiac ganglia on cardiodynamics and irANP release. In Sprague-Dawley rats, in vitro electrical stimulation of epicardial regions dense with cardiac ganglia (50Hz, 15-20μs, 4μA delivered in 5s trains), referred to as 'ganglionic' stimulation, resulted in a dramatic decrease in heart rate followed by a transient period of tachycardia. Cardiodynamic effects were accompanied by a significant increase in irANP release. Results from stimulation of epicardial regions lacking the presence of cardiac ganglia, termed 'non-ganglionic' stimulation indicated that heart rate changes were attributable to excitation of particular components of the ganglia at the site of stimulation, and not simply to spread of an electrical current over the epicardium. -- Also investigated were the effects of neonatal capsaicin treatment (capsaicin is a chemical that abolishes SP and CGRP cardiac innervation in rats when administered neonatally) on irANP release in the model of cardiac ganglia stimulation and in other models previously demonstrated to release irANP, such as stretch of the right atrium. In ganglionic stimulation experiments, release of irANP was independent of changes in heart rate. The presence of innervation by immunoreactive SP and CGRP was shown to be imperative for significant increase in irANP release after ganglionic stimulation and after stretch of the right atrium. -- Pharmacological studies were carried out to gain insight into the role of acetylcholine and noradrenaline in the biphasic change in heart rate and release of irANP after ganglionic stimulation. The initial decrease in heart rate was shown to be associated with parasympathetic innervation and similarly, tachycardia was associated with sympathetic innervation. However, release of irANP was demonstrated to be independent from either decreases or increases in heart rate. It is hypothesized that if SP and CGRP innervation are involved in irANP release, and if capsaicin depletes these peptides, then an acute treatment of capsaicin should release stores of SP and CGRP and yield an increased release of irANP. This was the case when vehicle-treated animals were administered an acute dose of capsaicin, however the tissues from animals treated neonatally with capsaicin showed no release of irANP. Acute capsaicin administration had no effect on heart rate in either group. -- Finally, Northern blot analysis of ANP messenger ribonucleic acid (mRNA) production was performed to ascertain if neonatal capsaicin treatment was affecting synthesis of ANP and if levels of mRNA expression were equivalent in vehicle- and capsaicin-treated animals. -- It was concluded that electrical stimulation of the intrinsic cardiac ganglia results in a biphasic change in heart rate associated with the sympathetic and parasympathetic cardiac innervation. Also, in the models used here, the SP and CGRP cardiac innervation seem responsible for the modulation of the release of irANP. Some preliminary data also suggest that SP and CGRP may be modulating irANP release in in vivo models of atrial pacing as well. Further studies are necessary before conclusions can be drawn regarding the effects of capsaicin on ANP synthesis. -- KEY WORDS and PHRASES: atrial natriuretic peptide; electrical stimulation of cardiac ganglia; atrial stretch; atrial pacing; substance P; calcitonin gene-related peptide; mRNA for ANP

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