naloxone and Hypertension--Renal

In order to study the role of opioid receptors in two models of experimental hypertension the binding of 3H-naloxone to membranes prepared from discrete brain regions and spinal cord was determined. Renal hypertensive rats (RHR) were found to have a greater density of 3H-naloxone binding sites in the hippocampus and hypothalamus when compared to spontaneously hypertensive rats (SHR) and normotensive Wistar rats (NR). The apparent dissociation constant (Kd) for 3H-naloxone binding did not differ between groups.

Topics: Analysis of Variance; Animals; Brain; Hypertension; Hypertension, Renal; Male; Naloxone; Rats; Rats, Inbred SHR; Reference Values; Tissue Distribution; Tritium

1. The effects of three opioid receptor agonists on the blood pressure and heart rate of anaesthetized normotensive, spontaneously hypertensive and renal hypertensive rats were measured. 2. Mu agonist morphiceptin i.c.v. induced a pressor response and increase in heart rate in hypertensive rats, but hypotension in normotensive rats. After intravenous (i.v.) injection, morphiceptin produced a hypotensive response in all three groups of rats. 3. In contrast, the delta agonist DTLET i.c.v. decreased blood pressure and heart rate in hypertensive rats, but increased both pressure and beat rate in normotensive rats. After i.v. injections DTLET produced a hypertensive response and increase in heart rate in all groups of rats. 4. Kappa agonist U-50, 488H given i.c.v. induced effects similar to morphiceptin: an increase in blood pressure and heart rate in hypertensive and a decrease in normotensive rats. After i.v. injections U-50, 488H produced decreases in blood pressure and heart rate in all treated groups of rats. 5. Pretreatment with naloxone antagonized the activity of morphiceptin but prevented only the stimulating effect of DTLET in normotensive rats. Cardiovascular actions of U-50, 488H were not blocked by naloxone. 6. The results suggest that opioid agonists exert similar changes in cardiovascular function at central and peripheral sites in both models of experimental hypertension and these effects are different in normotensive rats.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Amino Acid Sequence; Analgesics; Animals; Blood Pressure; Endorphins; Heart Rate; Hemodynamics; Hypertension, Renal; Injections, Intraventricular; Male; Molecular Sequence Data; Naloxone; Oligopeptides; Pyrrolidines; Rats; Rats, Inbred SHR; Rats, Inbred Strains

Central effects of naloxone on the cardiovascular responses of centrally administered clonidine were studied in anaesthetised normotensive, renal DOCA-salt hypertensive and morphine dependent rats. Clonidine (5 micrograms/ICV) produced significant decrease in blood pressure and heart rate in all the groups of rats in a dose dependent manner. Naloxone (2 micrograms/ICV) failed to reverse the responses of clonidine in all the rat groups. In morphine dependent normotensive and morphine dependent renal DOCA-salt hypertensive rats, the responses of clonidine were further enhanced in the presence of naloxone. Our observations clearly indicate that clonidine does not influence endogenous opioid system for producing cardiovascular effects.

Topics: Anesthesia; Animals; Blood Pressure; Clonidine; Desoxycorticosterone; Female; Heart Rate; Hypertension, Renal; Male; Morphine Dependence; Naloxone; Rats

The influence of blockade of endogenous opioids on the release of renin due to partial renal arterial constriction was determined acutely and chronically in unilaterally nephrectomized dogs. In acute preparations changes in plasma renin activity, arterial blood pressure, and heart rate were determined after 15 min of 60% renal arterial constriction before and after administration of either a saline vehicle, the opiate antagonist naloxone (0.05 mg/kg), or morphine (2 mg/kg). Acute antagonism of endogenous opiates abolished the increase in plasma renin activity and mean arterial pressure associated with renal arterial constriction. Repeated renal arterial constrictions in saline- or morphine-treated animals did not alter the humoral or hemodynamic responses. In chronic preparations long-term naloxone infusion attenuated the development of renovascular hypertension and diminished the increase in plasma renin activity. These data suggest that endogenous opioid peptides are modulators in the control of renin release and may be important participants in the pathogenesis of hypertension.

Topics: Animals; Blood Pressure; Dogs; Endorphins; Epinephrine; Heart Rate; Hypertension, Renal; Naloxone; Norepinephrine; Renin; Time Factors

Topics: Animals; Blood Pressure; Captopril; Hypertension, Renal; Injections, Intraventricular; Naloxone; Neurotensin; Nitroglycerin; Proline; Rats; Rats, Inbred Strains; Thyrotropin-Releasing Hormone

Experimental and genetic hypertension in male rate is accompanied by a lower specific [3H]naloxone binding in the dorsal horn of the spinal cord, and in the hippocampus as compared to controls. Rats which are genetically resistant to hypertensive stimuli have a higher specific [3H]naloxone binding in the nucleus tractus solitarius and lower opiate receptor binding in the dorsal horn. Together with previous studies which demonstrated a correlation between blood pressure and pain sensitivity, these results support the notion that specific brain loci participate in co-regulation of pain perception and blood pressure.

Topics: Animals; Atrophy; Brain; Cell Membrane; Hippocampus; Hypertension, Renal; Kidney; Kinetics; Male; Naloxone; Organ Specificity; Rats; Rats, Inbred Strains; Receptors, Opioid; Spinal Cord

Pain sensitivity was studied in renal and DOCA-salt hypertensive rats, and in two strains of rats derived from the same parental strain for their sensitivity (H) or immunity (N) to hypertension induced by DOCA-salt treatment. Experimentally hypertensive rats, and H and N rats were less sensitive to painful stimuli than their appropriate controls, as assessed in the hot-plate and paw pinch tests. Naloxone reversed this hypoalgesia in both experimentally and genetically hypertensive rats while it did not affect blood pressure in any rat-type tested. Opioid activity was measured with the radioreceptor assay in several brain regions and pituitary gland of both experimentally and genetically hypertensive rats. Experimentally hypertensive rats had a 45% higher level of opioid activity in the spinal cord compared to control. Rats of the H and N strains both exhibited higher levels of opioid activity in the spinal cord, hypothalamus and pituitary. It is suggested that control systems for blood pressure and pain sensitivity are closely associated in the rat.

Topics: Animals; Blood Pressure; Brain; Desoxycorticosterone; Enkephalins; Hypertension; Hypertension, Renal; Male; Naloxone; Pain; Pituitary Gland; Rats; Receptors, Opioid; Spinal Cord

Topics: Animals; Blood Pressure; Hypertension, Renal; Male; Naloxone; Nociceptors; Rats; Receptors, Opioid; Sensory Thresholds