enkephalin--leucine-2-alanine and Hypertension

To investigate the cardiovascular effects of microinjection into the hippocampus of selective mu, delta and kappa opioid receptor agonists in anesthetized spontaneously hypertensive rats, isolation-induced hypertensive rats and their normotensive Wistar-Kyoto and group-housed Sprague-Dawley controls.. The microinjection of a selective kappa agonist, spiradoline mesylate, (+/-)-(5alpha, 7alpha, 8beta)-3,4-dichloro-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro++ +[4.5]dec-8-yl]-benzeneacetamide mesylate) (5 nmol) into the dorsal region of hippocampus, where injection of control saline failed to affect cardiovascular activities, induced centrally mediated decreases in mean blood pressure and heart rate in both hypertensive and normotensive rats. The effects were blocked by prior treatment of the hippocampus with nor-binaltorphimine dihydrochloride, a selective kappa opioid receptor antagonist The hypotensive and bradycardic effects were quantitatively similar between spontaneously hypertensive rats and Wistar-Kyoto rats and between isolated hypertensive rats and normotensive group-housed rats. The sequential administration of increasing doses (5, 10, 50 nmol) of the selective mu agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin and delta agonists [D-Ala2, D-Leu5]-enkephalin or [D-Pen2, D-Pen5]-enkephalin into the same areas of the hippocampus as used for the kappa agonist had no significant effects on mean blood pressure and heart rate in either hypertensive or normotensive rats.. The present results extend our previous findings of a hippocampally mediated hypotensive effect of kappa agonists in the spontaneously hypertensive rat to the isolated rat model of hypertension and they establish that mu and delta opioid receptor agonists similarly applied are ineffective. Hippocampal kappa receptors may have a greater role in cardiovascular control than mu and delta receptors.

Topics: Analgesics; Animals; Cardiovascular System; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, D-Penicillamine (2,5)-; Enkephalin, Leucine-2-Alanine; Enkephalins; Hippocampus; Hypertension; Male; Opioid Peptides; Pyrrolidines; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Sprague-Dawley; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu

The level of urinary excretion of catecholamines (CA) and their precursors was studied in 87 patients with stage I, II hypertensive disease (HD). Three groups were formed depending on the therapy option: group I comprised stage I HD patients in whom endonasal dalargin electrophoresis (EDE) was instituted, groups II and III were patients with stage II HD who were given a complex therapy with captopril plus EDE and monotherapy with captopril respectively. EDE led to a decline in the functional activity of the sympathoadrenal system (SAS) in stage I HD patients and potentiated a hypotensive effect of captopril resulting in diminution of excretion of norepinephrine. Captopril monotherapy failed to have an effect on the SAS condition.

Topics: Adrenal Glands; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Captopril; Drug Synergism; Drug Therapy, Combination; Enkephalin, Leucine-2-Alanine; Humans; Hypertension; Middle Aged; Sympathetic Nervous System

To assess effectiveness of blood hypertension treatment with inhibitors of angiotensin converting enzyme and calcium channels blocker.. 83 outpatients with mild and moderate blood hypertension received monotherapy with prestarium, anap and lomir for 12 months. The trends in parameters of blood pressure, total peripheral vascular resistance, thickness of the interventricular septum and left ventricular posterior wall were estimated.. Long-term effective monotherapy with prestarium, anap and lomir was possible in 47, 62 and 45% of the patients, respectively. Diastolic pressure lowered by 25, 24 and 25%, total peripheral vascular resistance reduced by 20, 19 and 22%, respectively. The three drugs produced similar positive effects on left ventricular thickness, had no negative effects on bioelectric activity of the heart, clinical and biochemical blood counts.. Prestarium, anap and lomir are effective against hypertension and diminish left ventricular hypertrophy in hypertensive patients.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Azides; Blood Pressure; Calcium Channel Blockers; Echocardiography; Enkephalin, Leucine-2-Alanine; Female; Follow-Up Studies; Heart Ventricles; Humans; Hypertension; Indoles; Isradipine; Male; Middle Aged; Perindopril; Treatment Outcome; Vascular Resistance

Brief (7-14 days) social deprivation stress has been found to increase blood pressure in Wistar rats, an effect dependent on activation of opioid function. The role of central opioids in this and other responses to stress has been repeatedly determined, but the possible involvement of modifications of peripheral opioid mechanisms is poorly understood. To further increase this knowledge, we have examined the opioid sensitivity of tail arteries taken from social deprived Wistar rats by studying the effect of beta-endorphin and DADLE "in vitro". Both opioids inhibited the electrically-induced constriction of the preparations in a dose-dependent manner, but these actions were significantly attenuated after 7-14 days of social deprivation. When the rats were isolated for 30-35 days, the hypertensive response was still present but the arteries from group-housed and isolated animals no longer showed differential sensitivity to opioids. This difference with respect to 7-14 days of isolation could be related to age-dependent changes of opioid function, which were observed among group-housed animals. The results suggest that social deprivation stress induces an adaptation of the tail arteries to the opioid effects on contractility. It is suggested that this endogenous adaptation could be contributing to the hypertensive response observed after social deprivation.

Topics: Adaptation, Physiological; Animals; beta-Endorphin; Dose-Response Relationship, Drug; Enkephalin, Leucine-2-Alanine; Hypertension; Male; Naloxone; Narcotic Antagonists; Narcotics; Rats; Rats, Wistar; Receptors, Opioid; Social Isolation; Stress, Physiological; Tail; Vasoconstriction

To determine whether the peripheral opioid system participates in hypertension development we studied responses to various opioid receptor agonists in field-stimulated isolated tail artery segments taken from spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats at different ages. The mu-selective agonist (DAGO) and the delta-selective D-Ala2-D-Leu5-enkephalin (DADLE) both suppressed the electrically stimulated vasoconstriction (EIC), but only in SHR arteries. The mu-selective antagonist beta-funaltrexamine reversed the effects of both DAGO and DADLE. Since the delta-selective antagonist ICI-174864 did not block DADLE inhibition, it is likely that both DAGO and DADLE effects were mu-receptor-mediated. Effects of DAGO and DADLE were qualitatively and quantitatively similar at all ages of SHR tested, and were not temporally related to hypertension development. Dynorphin (1-13) (DYN), a kappa-agonist, increased basal tone and EIC in all three rat strains. These responses were not blocked by nor-binaltorphimine, a selective kappa-opioid antagonist, suggesting that they may not involve kappa-receptor activation. There was a greater sensitivity to DYN at younger ages in all three rat strains and the sensitivity decreased with age. At 16 weeks when SHR hypertension was fully developed, SHR tail artery became almost totally insensitive to DYN in contrast to the continued responsiveness of 16-week-old WKY and SD arteries. The diminished effects to DYN in 16-week-old SHR tail arteries is suggestive of a compensatory mechanism to the hypertensive state. Collectively, the results establish that opioid receptor responses in SHR tail artery differ from those of normotensive rats. The significance of these differences to hypertension development in SHR remains to be determined.

Topics: Age Factors; Animals; Dose-Response Relationship, Drug; Dynorphins; Electric Stimulation; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine-2-Alanine; Enkephalins; Hypertension; In Vitro Techniques; Male; Naltrexone; Narcotic Antagonists; Phenylephrine; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Sprague-Dawley; Receptors, Opioid; Tail; Vasoconstriction

Naloxone enantiomorphs were given intracerebroventricularly (i.c.v.) to rats socially deprived for a brief period of time (7-14 days) in order to ascertain the mediation of central opiate receptors in the reversal effect of opiate antagonists on the high systolic blood pressure induced by this type of stress. While the active enantiomorph ((-)-naloxone, 20 nmol per rat) lowered the elevated blood pressure, the (+)-enantiomorph (which shows a 10,000-fold lower affinity for opiate receptors) had no effect. Additionally, the antihypertensive effect induced by i.c.v. administration of an antagonist of the mu-opiate receptor (beta-funaltrexamine, 20 nmol per rat), but not of the delta-opiate receptor (ICI 174,864, 15 nmol per rat) pointed to the involvement of mu-opiate receptors as the endogenous component of the hypertensive response of rats to stress.

Topics: Animals; Blood Pressure; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Enkephalins; Hypertension; Injections, Intraventricular; Male; Naloxone; Naltrexone; Narcotic Antagonists; Rats; Rats, Inbred Strains; Receptors, Opioid; Social Isolation; Stereoisomerism; Stress, Psychological

Dalargin, a small regulatory peptide produced in the USSR was tested with respect to its effect on psychological indices in 80 patients with essential hypertension grades I and II. Endonasal Dalargin electrophoresis was applied in 50 patients and 30 were subjected to endonasal galvanization (the control group). Electrophoretically applied Dalargin was shown to accelerate the sensorimotor responses, improve memory, reduce the anxiety levels.

Topics: Adult; Anxiety Disorders; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Female; Humans; Hypertension; Iontophoresis; Male; Memory Disorders; Middle Aged; Neurocognitive Disorders; Psychomotor Performance