A. !, FADEN, K. KRAFr, and K. O. STUMPE Following the discovery of the pentapeptide enkephalins in 1975, a number of endogenous opioid peptides and opiate receptors have been identified. Endogenous opioids and opiate-receptor mechanisms have been implicated in a variety of regulat ory and dysregulatory functions including analgesia, cardiovascular regulation, shock, hypertension, traumatic spinal cord and brain injury, stroke, immune func tion, feeding behavior, diuresis, gastrointestinal motility, and respiratory control, among others. Over the past 10 years, many studies have demonstrated a relationship between endogenous opioids and the cardiovascular system under both homeostatic and pathophysiological conditions. Opioids and opiate receptors have been found in various cardioregulatory sites within the brain and spinal cord, as well as in peripheral tissues such as sympathetic ganglia, adrenal gland, and heart. Both endogenous opioids and exogenous opiates have been shown to produce potent cardiovascular effects following central nervous system or systemic administration. Opiate-receptor antagonists have been demonstrated to reverse hypotension from sepsis, hypo volemia, and anaphylaxis; such studies have been used to infer activity of endogenous opioid systems in shock. Changes in tissue concentrations of endogenous opioids and! or opiate receptors have been found after shock and hypertension, further implying a role for opioid systems in the etiology of these conditions. In addition, modification of opiate receptor regulation, receptor binding, or opioid metabolism has also been used to establish a potential role for endogenous opioid systems in cardiovascular control and dyscontrol.

Endogenous Opioids and Cardiovascular Regulation: Introduction

Anatomy
Distribution of Opioid Peptides Functionally Related to the Cardiovascular System
Studies on Enkephalinergic Mechanisms in Cardiovascular Centers of the Medulla Oblongata of the Rat and their Interactions with Centrally Administered Neuropeptide Y
Multiplicity of Opioidergic Pathways Related to Cardiovascular Innervation: Differential Contribution of All Three Opioid Precursors
Physiology
Opioids, Opiate Receptors, and Central Cardiovascular Regulation
Adrenergic Opioid Interaction in the Brain Stem: Role in Cardiovascular Regulation
Influence of the Opioid System on Sympathetic Activity and the Renin-Aldosterone System in Healthy Males
Role of Leu-morphin, an Opioid Peptide, in the Central Regulation of Fluid Balance and Blood Pressure in Rats
Endogenous Opioids in the Dorsal Vagal Complex and Resting Cardiovascular Function in the Anesthetized Rat
Influence of Opiate Peptides on Blood Pressure Regulation and on Hypothalamic Blood Flow
Opioid Peptides in Human Adrenal Medulla: Their Role in the Modulation of Catecholamine Secretion
Cardiovascular Effects of Neuropeptide Y in the Caudal Ventrolateral Medulla
Plasma Met-enkephalin and Cardiovascular Responses to Stress
Pharmacology
Opioid Receptors in the Sympathetic Supply to Blood Vessels and the Heart
Interactions of Opioid Peptides and Adrenergic Agents in the Regulation of Blood Pressure
Effect of Opiate Receptor Blockade on the Cardiovascular and Plasma Noradrenaline Response to Intravenous Tyramine in Man
Effects of Mu- and Delta-Opiate Receptor Agonists on Systemic and Regional Hemodynamics in Conscious Rats
Retardment of Development of Hypertension in the Spontaneously Hypertensive Rat by Long-Term Kappa-Opioid Receptor Antagonism
Naltrexone Inhibits Alpha-Methydopa-Induced Hypotension in a Dose-Dependent Manner
Effects of 17-alpha-estradiol, a Possible Endogenous Opiate Antagonist, on Cardiovascular Responses in Conscious Unrestrained Rats
Opioid Receptor Types at Noradrenergic Neurons and their Roles in Blood Pressure Regulation
Effect of Opioids on Plasma Levels of Immunoreactive Atrial Natriuretic Factor
Production by Systemic Enkephalin of Hemodynamic Effects by Afferent Modulation of Autonomic Nervous System Tone
Pathophysiology and Clinical Aspects
Endogenous Opioids in the Pathophysiology of Shock: Sites of Action, Autonomic Involvement, and Receptor Interactions
Endogenous Opioids and Blood Pressure in Man
Effects of Hemorrhagic Shock on Plasma Met-enkephalin, Vasopressin, Catecholamines, and Cardiovascular Functions in Intact and Adrenalectomized Dogs
Effect of Hypertension on the Response of Plasma Beta-Endorphin to the Cold Pressor Test
Normalization by Clonidine of Reduced Plasma Beta-endorphin and Leu-enkephalin Concentrations and Elevated Blood Pressure in Young Patients with Mild Essential Hypertension
Role of Opioids in the Pathophysiology of Hypertension
Effect of Low Dosage of Naloxone on Clonidine-Induced Changes in Blood Pressure, Catecholamines, Renin, and Aldosterone in Essential Hypertension
Effect of Lisinopril on Circulating Neuropeptides in Essential Hypertensive Patients
Endogenous Opioids and Reversal of Renovascular Hypertension
Comparison of Pain Threshold as Assessed by Tooth Pulp Stimulation in Normotensives with Different Hypertensive Hereditary Backgrounds and in Borderline and Established Hypertensives.