Cardiovascular Effects of Endogenous Opiate Systems

Abstract

FurtherANNUAL REVIEWS (7,(22)(23)(24). Rather, I attempt to provide a theoretical framework within which to construct novel insights into this rapidly developing area, and discuss certain pitfalls in opiate-cardiovascular studies. BRIEF REVIEW OF CENTRAL AUTONOMIC-CARDiOVASCULAR PATHWAYSInformation regarding peripheral hemodynamic changes is detected by mechanoreceptors in the major arteries and relayed via vagal afferents to the brainstem. Stimulation of chemoreceptors, such as pulmonary "J" receptors found in the alveoli of the lung adjacent to pulmonary capillaries (25), can also result in the detection of changes in cardiorespiratory vari ables, which are likewise relayed via the ninth and tenth cranial nerves to Annu. Rev. Pharmacol. Toxicol. 1983.23:541-541. Downloaded from www.annualreviews.org by University of Nebraska -Lincoln on 09/19/13. For personal use only. .... ----------------I /SPLANCHNIC � . D " ME . EPI. NOREPI, · ENKEPH.Figu re J Central and peripheral autonomic pathways are represented in this simplified schematic of the neuronal circuitry that regulates cardiovascular responses. Solid lines gener ally represent parasympathetic innervations; dashed lines indicate pathways with greater direct relevance to sympathetic integration. The hypothalamus alone contains at least nine different nuclei with different anatomical and functional relationships among each other and with other autonomic nuclei. For a complete reference, see (26). Abbreviations AMYG Amygdala NTS Nucleus tractus solitarius LRN Lateral reticular nucleus LC Locus coeruJeus HYP Hypothalamus (many nuclei) ILN Intermediolateral nucleus Ji-ENDOR Beta endorphin EPI Epinephrine ENKEPH Enkepha1in DVN Dorsal vagal nucleus NA Nucleus ambiguus X Vagus nerve IX Ninth cranial nerve DYNOR Dynorphin NOREPI Norepinephrine AD MED Adrenal medulla Annu. Rev. Pharmacol. Toxicol. 1983.23:541-541. Downloaded from www.annualreviews.org by University of Nebraska -Lincoln on 09/19/13. For personal use only.

Effects of morphine on catecholamine release and arrhythmias evoked by myocardial ischaemia in rats

“…Animal experiments have also shown differing haemodynamic effects, depending on route of administration, dose, and the additional effects of anaesthetics (Fennessy & Rattray, 1971;Holaday, 1983). In our experiments, morphine administration led to significant increases in MAP.…”

Opioids in the systemic hemodynamic and renal responses to stress in spontaneously hypertensive rats.

“…In this manner, the arterial hypotension of endotoxic, circulatory, and hemorrhagic shock have been shown to be antagonized by blockade of opioid receptors with naloxone. 26 Although the mechanism by which opioids are involved in these shock models is not completely defined, the models serve to illustrate that endogenous opioid systems may contribute to the changes in mean arterial pressure and heart rate when normal cardiovascular function is altered.…”

Regional haemodynamic effects of μ‐, δ‐, and κ‐opioid agonists microinjected into the hypothalamic paraventricular nuclei of conscious, unrestrained rats

“…There is accumulating evidence to suggest a role for endogenous opioid peptides in central cardiovascular control (Holaday, 1983;Feuerstein, 1985;Feuerstein & Siren, 1987;Siren & Feuerstein, 1992). Mainly, opioid peptides and opiate receptors have been found in specific brain nuclei, with an established role in the regulation of cardiovascular activities (Atweh & Kuhar, 1977;Hokfelt et al, 1977;Fallon & Leslie, 1986;Mansour et al, 1988;Desjardins et al, 1990), and potent cardiovascular effects have been reported following central administration of opioid peptides (Hassen et al, 1983;Pfeiffer et al, 1983a,b;Appel et al, 1986;Kiritsy-Roy et al, 1986;Marson et al, 1989a,b;May et al, 1989;Siren et al, 1989;Jin & Rockhold, 1991;Siren & Feuerstein, 1991).…”

“…Mainly, opioid peptides and opiate receptors have been found in specific brain nuclei, with an established role in the regulation of cardiovascular activities (Atweh & Kuhar, 1977;Hokfelt et al, 1977;Fallon & Leslie, 1986;Mansour et al, 1988;Desjardins et al, 1990), and potent cardiovascular effects have been reported following central administration of opioid peptides (Hassen et al, 1983;Pfeiffer et al, 1983a,b;Appel et al, 1986;Kiritsy-Roy et al, 1986;Marson et al, 1989a,b;May et al, 1989;Siren et al, 1989;Jin & Rockhold, 1991;Siren & Feuerstein, 1991). However, pharmacological studies with opioid ligands have revealed a complex pattern of cardiovascular responses, which has been attributed to the multiple opioid receptors, the type of opioid ligand and its selectivity toward specific opioid receptor, the state of consciousness of the experimental animals, the site(s) of injection and dosage, species, and experimental conditions (i.e., stressed versus resting animals) (Holaday, 1983;Feuerstein, 1985).…”