Modulation of Sympathetic Actions on the Heart by Opioid Receptor Stimulation

Abstract

The sympathetic nervous system, the most important extrinsic regulatory mechanism of the heart, is inhibited postsynaptically and presynaptically by opioid peptides produced in the heart via their respective receptors. The cardiac actions of β-adrenergic receptor (β-AR) stimulation are attenuated by activation of the opioid receptor (OR) with OR agonist at ineffective concentrations, implying cross-talk between the OR and β-AR. This cross-talk results from inhibition of the Gs protein and adenylyl cyclase of the β-AR pathway by the pertussis toxin-sensitive G protein of the opioid pathway. Alterations in cross-talk between these two receptors occur in pathological situations to meet bodily needs. In myocardial ischemia, when the sympathetic activity is increased, the inhibition of β-AR stimulation by ĸ-opioid stimulation is also enhanced, thus reducing the workload, oxygen consumption and cardiac injury. Whereas cardiac responsiveness to sympathetic discharges is also reduced after chronic hypoxia, the cross-talk between ĸ-OR and β-AR is reduced to prevent undue suppression of the sympathetic influence on the heart. On the other hand, impairment of the cross-talk may result in abnormality. A lack or a significant reduction in the inhibition of β-AR stimulation by ĸ-OR stimulation may lead to an excessive increase in cardiac activities, which contribute to the maintenance of high arterial blood pressure in spontaneously hypertensive rats. Other than opioid peptides, female sex hormone and adenosine also inhibit the sympathetic actions on the heart. In addition, sympathetic action is also inhibited presynaptically by ĸ-opioid peptides via their receptor.

Negative inotropic and chronotropic effects on the guinea pig atrium of extracts obtained from Averrhoa carambola L. leaves

“…In heart muscle, stimulation of opioid (µ, κ, and δ) or muscarinic (M 2 ) receptors may mediate a reduction in cardiac contractility (16)(17)(18)(19), a result that can also be obtained by activating the ß 3 -adrenoceptor. This effect involves the nitric oxide synthase pathway (20,21).…”

Physiological and Clinical Implications of Adrenergic Pathways at High Altitude

“…An impairment of norepinephrine intravesicular uptake in hypoxia could also contribute to increase the concentration of norepinephrine in the synaptic space and contribute to the desensitization of the adrenergic pathway [ 26 , 36 ]. Opioid receptors can also be involved since a cross-talk exists between these receptors and β-AR: the pertussis toxin-sensitive G protein of the opioid pathway inhibits the Gs protein of the adrenergic pathway [ 51 ]. The Fig.…”

Involvement of endogenous opioid peptides and nitric oxide in the blunted chronotropic and inotropic responses to β‐adrenergic stimulation in cirrhotic rats

“…It is well known that the endogenous opioid peptides are involved in the regulation of the cardiovascular system through both the peripheral and central receptors. Besides modulating the autonomic nervous system [26], they have been demonstrated to have effects on the cardiac rhythm [19] and contractility [20]. Abnormalities of the endogenous opioid peptides system have been reported in several pathophysiological conditions in both human and animal models of cardiovascular diseases such as acute or chronic heart ischemia and genetic hypertension [27][28][29].…”

“…It seems that some of these actions are mediated through the endogenous opioid peptides' inhibitory effect on the sympathetic nervous system [22]. This inhibition is mainly achieved by suppressing the signaling pathway of the b-adrenergic receptor [22][23][24][25], the dominant receptor that mediates the action of sympathetic stimulation in the heart [26]. The importance of this inhibitory effect is best illustrated by its alteration in different pathophysiological situations [27][28][29].…”