naloxone and Hypertension--Renovascular

Opiates are now known to be important modulators of cardiovascular function in both the normotensive and hypertensive states. There is accumulating evidence that endogenous opiates are elevated in models of hypertension of various etiologies including genetic and renovascular hypertension. Early evidence for elevated opiates in hypertension arose from observations that hypertensive humans and rats with genetic or experimental hypertension exhibited hypoalgesia in various tests of pain sensitivity. Because pain and cardiovascular regulatory systems have in common a number of brain loci, cardiovascular effects of opiates and opiate blockade were studied. These studies have shown that opiate blockade can attenuate the development of hypertension and reduce blood pressure in chronic hypertension possibly via actions on the baroreflexes and/or by modulating the centrally mediated pressor actions of angiotensin II.

Topics: Angiotensin II; Animals; Blood Pressure; Cardiovascular System; Endorphins; Hypertension; Hypertension, Renovascular; Models, Cardiovascular; Naloxone; Narcotics; Pain; Pressoreceptors; Shock

The apelin/APJ system has an important role in the regulation of vascular tone and blood pressure. Opioid receptors (OPRs) are also important cardiovascular regulators and exert many of their effects by modulating the function of other G-protein-coupled receptors. The aim of this study was to analyze the interaction of apelin and the opioid system with respect to vascular responses to apelin in rats with renovascular hypertension (two-kidney, one clip (2K1C)). Homodynamic studies were carried out in 2K1C rats. Naloxone (a nonselective OPR inhibitor) or nor-binaltorphimine dihydrochloride (norBNI, a kappa OPR inhibitor) and signaling pathway inhibitors PTX (a Gi path inhibitor) and chelerythrine (a protein kinase C (PKC) inhibitor) were administered before apelin at 20 and 40 μg kg

Topics: Animals; Antihypertensive Agents; Apelin; Benzophenanthridines; Dose-Response Relationship, Drug; Enzyme Inhibitors; Hemodynamics; Hypertension, Renovascular; Male; Naloxone; Naltrexone; Narcotic Antagonists; Protein Kinase C; Rats; Rats, Wistar; Receptors, Opioid

10 patients with renovascular hypertension (HRV) and 12 healthy persons were examined under water immersion (WI) conditions without and after blockade of opioid receptors with 2 mg of naloxone. Blood pressure, body mass, change of plasma volume, plasma molality, PRA, and serum values of AVP, aldosterone and catecholamines were evaluated. There were no significant changes between the two examined groups before and after WI. It seems that the drop in blood pressure induced by WI is not only the result of diminished activation of RAAS. The role of opioid receptors in controlling blood pressure and other evaluated parameters is likely in both examined groups.

Topics: Adult; Aldosterone; Body Height; Body Weight; Case-Control Studies; Catecholamines; Female; Humans; Hypertension, Renovascular; Immersion; Male; Naloxone; Narcotic Antagonists; Osmolar Concentration; Plasma Volume; Renin-Angiotensin System; Vasopressins

These experiments were designed to determine if the opiate antagonist naloxone affects vascular sensitivity in 2K-1C hypertensive rats. Group 1 was 2K-1C hypertensive rats. Group 2 was 2K-1C rats given a naloxone infusion (100 micrograms/h) for 14 days. Group 3 received naloxone without clipping. Group 4 was untreated rats. At day 14 following clipping, systolic blood pressure was increased significantly in the 2K-1C rats. Those infused with naloxone showed a significant attenuation of the increase in blood pressure. Vascular responses to norepinephrine and KCl in the aortae from all groups were tested. Strips from untreated, 2K-1C rats were more sensitive to the contractile effects of norepinephrine than those from naloxone-treated, 2K-1C rats, and from both groups of normotensive rats. Contractile responsiveness to depolarizing concentrations of KCl were not different among the four groups. These data demonstrate that naloxone attenuates the development of renal hypertension and prevents the increase in vascular responsiveness to norepinephrine.

Topics: Angiotensin II; Animals; Blood Pressure; Central Nervous System; Hypertension, Renovascular; In Vitro Techniques; Male; Naloxone; Norepinephrine; Rats; Rats, Inbred Strains; Vasoconstriction

The present experiments were designed to determine if an opiate antagonist affects blood pressure in two-kidney one-clip Goldblatt rats. Male Sprague-Dawley rats were divided into three groups. Group 1 received an infusion of saline intraperitoneally via an osmotic pump and left renal artery constriction (RAC). In group 2, rats were treated the same as group 1, except that they received an intraperitoneal infusion of naloxone (100 micrograms/h). Group 3 received the same infusion of naloxone without RAC. Naloxone-infused Goldblatt rats showed a significantly lower systolic blood pressure (SBP) than saline-infused Goldblatt rats (132 +/- 7 vs. 160 +/- 9 mmHg at day 14), but a higher SBP than control (132 +/- 7 vs. 106 +/- 1 mmHg). Infusion of naloxone did not significantly change SBP in normotensive rats. Renal renin activity in the clipped kidney was higher than in the nonclipped kidney in groups 1 and 2. Plasma renin activity (PRA) in both groups of Goldblatt rats was higher than in group 3, but no significant difference was found between the two groups of Goldblatt rats (groups 1 and 2). Naloxone (1.5 microM) did not affect the basal secretion of renin by isolated cortical slices from untreated rats. The present data demonstrate that naloxone significantly attenuates the development of hypertension in two-kidney one-clip rats. The attenuation of blood pressure was not associated with the changes in PRA, renal renin activity, or plasma aldosterone concentrations. The data support the hypothesis that the endogenous opioid system may be involved in the development of renovascular hypertension.

Topics: Aldosterone; Animals; Blood Pressure; Heart Rate; Hypertension, Renovascular; Male; Naloxone; Rats; Rats, Inbred Strains; Reference Values; Renin

It is evident that hypertension is associated with elevated endogenous opiates. This study was designed to examine the role of endogenous opiates in the development and/or maintenance of two-kidney renovascular hypertension and in baroreceptor reflex function in conscious hypertensive rats. Naloxone administration during the onset of hypertension significantly attenuated the rise in blood pressure. After one week, systolic blood pressure in naloxone-treated rats was 27 mmHg lower than in 0.9% NaCl-treated hypertensive rats. Acute naloxone infusions in chronic hypertensive animals also significantly lowered blood pressure (-10%) and heart rate (-26%). Baroreceptor function was significantly enhanced in both normotensive (+135%) and hypertensive (+207%) rats after administration of naloxone. Furthermore, naloxone treatment also caused the baroreflex response to shift from the higher reset state toward that seen in normotensive counterparts. The inability of naloxone methyl bromide to alter baroreflex sensitivity indicates that the site(s) of action of opiates resides in the brain. These data support a role for opiates in the development and/or maintenance of renovascular hypertension, which may be related to alterations in baroreceptor reflex function.

Topics: Animals; Blood Pressure; Endorphins; Heart; Hypertension, Renovascular; Male; Naloxone; Phenylephrine; Pressoreceptors; Rats; Rats, Inbred Strains

The rapid fall in blood pressure after removal of the constricting clip in two-kidney one-clip (2K-1C) hypertension in the rat is not fully explained by inhibition of the renin-angiotensin system or change in sodium balance. It has been postulated that compounds released in the renal venous effluent following unclipping of 2K-1C rats have a central opiate-like action and endogenous opioids are recognized to have profound hypotensive properties. To investigate this, we removed the clip from, or performed a sham operation in, early phase (less than 6 weeks) 2K-1C hypertensive rats during an infusion of naloxone, an opioid antagonist, or vehicle alone. The infusion of naloxone did not affect the pattern of blood pressure fall in either unclipped or sham-operated rats. Both naloxone-treated and control groups were similarly normotensive at 24 hr postoperation, the MAP being significantly lower than in the sham-operated groups, which regained previously hypertensive levels. Heart rate was unchanged 24 hr postoperatively in all groups. Morphine-induced bradycardia and hypotension were significantly reduced by naloxone infusion. Thus, naloxone infusion had no effect on blood pressure or heart rate in either the sham-operated or the unclipped groups, indicating that endogenous opioids do not have a major role in the reversal of renovascular hypertension under these circumstances.

Topics: Animals; Blood Pressure; Female; Heart Rate; Hypertension, Renovascular; Morphine; Naloxone; Rats; Renin