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Biomedical subjects

G Feuerstein

Publications and source records attributed to G Feuerstein.

At least 217 records · Page 12Linked to original sources
PubMed1984

Central cardiovascular effects of vasotocin, oxytocin and vasopressin in conscious rats.

Arg8-vasotocin (AVT), oxytocin and Arg8-vasopressin (AVP) were injected into the i.c.v. space and/or the hypothalamus of awake, freely moving rats in order to investigate the potential role of these neuropeptides in central cardiovascular control. AVT (0.015-10 nmol) injected i.c.v. caused dose-dependent pressor responses; low doses also elicited tachycardia, whereas the higher doses (1 and 10 nmol) produced bradycardia. In contrast, oxytocin injections into the lateral ventricle (0.015-100 nmol) had no significant cardiovascular effects. Plasma vasopressin was not affected by i.c.v. administration of oxytocin or AVT except at the highest dose of AVT. AVT (0.1 or 1 nmol) and AVP (0.015 or 0.1 nmol) injected into the hypothalamic nucleus preopticus medialis (POM) increased blood pressure and heart rate; these changes were much greater than with comparable doses of AVT injected i.c.v. Plasma levels of norepinephrine and epinephrine, but not vasopressin, were significantly elevated during the pressor period induced by 1 nmol of AVT injected into the POM. The pressor and cardiac accelerating effects of AVT (1 nmol) injected into the POM were significantly diminished in bilaterally adrenal demedullated, bretylium-treated rats. These data suggest a role for AVT, but not oxytocin, in central cardiovascular control through activation of the sympathoadrenomedullary axis. The anteroventral hypothalamus might play a central role in these autonomic effects of vasotocin. It is also suggested that AVP and AVT share some central autonomic effects due to similarities in the side-chain of their molecules.

Animals↗
PubMed1983

Effects of FPL-55712 or indomethacin on leukotriene-induced coronary constriction in the intact pig heart.

Intracoronary leukotriene D4, 0.1-3.0 micrograms (0.2-6.0 nmol), produced dose-dependent decreases in coronary flow of anesthetized pigs. Pretreatment with intracoronary FPL-55712 (0.1, 0.3 and 1.0 mg) reduced coronary constriction due to 1.0 micrograms leukotriene D4 by up to 77%. FPL-55712 did not produce sustained alterations in coronary flow, left ventricular end-diastolic pressure, systemic arterial pressure, or heart rate. Indomethacin pretreatment (6 mg/kg i.v.) had no effect on leukotriene-induced coronary constriction. Inhibition produced by FPL-55712 may be useful in disease states involving leukotriene-mediated coronary constriction.

Animals↗
PubMed1983

Coronary constriction by leukotriene C4, D4, and E4 in the intact pig heart.

Leukotrienes are naturally occurring vasoactive metabolites of arachidonic acid that increase during inflammatory reactions and anaphylaxis. Coronary constriction and reduced myocardial contractility after leukotriene C4 and D4 administration were demonstrated in the isolated guinea pig heart. To explore the effects of leukotrienes in the in situ, blood-perfused heart, we administered leukotrienes C4, D4, and E4 into the coronary artery of the domestic pig. Increasing doses (0.1, 0.3, 1.0, and 3.0 micrograms) of leukotrienes C4, D4, and E4 were injected into the left anterior descending coronary artery of 8 open-chest domestic pigs. Significant dose-related reduction in coronary blood flow was observed after each leukotriene administration. Three micrograms of each leukotriene produced the following maximal decreases (mean +/- standard error); C4 = 80 +/- 9%, p less than 0.001; D4 = 81 +/- 3%, p less than 0.001; E4 = 64 +/- 12%, p less than 0.005. In several instances, surface electrograms recorded from the myocardial region exposed to leukotrienes showed signs of focal myocardial ischemia, sometimes accompanied by ventricular arrhythmia. Significant elevation of left ventricular end-diastolic pressure was observed after large doses (1 or 3 micrograms) of leukotrienes C4 and D4. Minimal (5 to 10%) decreases in mean arterial pressure and no change in heart rate were observed after leukotriene injection. We conclude that leukotrienes C4, D4, and E4 are extremely potent coronary constrictors in the in situ heart. The intensity of response and associated electrocardiographic signs of ischemia suggest that constriction is mainly due to a primary effect on vascular smooth muscle. However, coronary flow reduction may also reflect consequences of a primary negative inotropic action. Leukotrienes may play a significant role in the pathogenesis of a variety of cardiac disorders, particularly those associated with extensive inflammatory changes.

Animals↗
PubMed1983

Alteration of leukotriene D4 hypotension by thyrotropin releasing hormone.

Leukotriene D4 (LTD4), a component of slow reacting substance of anaphylaxis (SRS-A)1, produces marked hypotension in laboratory animals2,3, implicating it as a potential mediator of anaphylactic shock. It has been demonstrated that naloxone reverses the hypotension associated with endotoxaemia4-6, hypovolaemia7,8 and spinal injury9,10, presumably through blockade of endogenous opioid systems11. More recently, it has also been shown that thyrotropin releasing hormone (TRH) improves experimental shock12 and spinal injury13, and it has been postulated that TRH acts by 'physiological' antagonism of endogenous opioid systems in these conditions. Here we report that TRH both blocked and reversed leukotriene-induced hypotension in the unanaesthetized guinea pig, whereas naloxone had no effect. LTD4 hypotension was also reversed by intracerebroventricular (i.c.v.) administration of TRH at a dose that had no effect when given systemically. LTD4 administration was associated with sympatho-adrenomedullary activation, and TRH further augmented this response. Peripheral cholinergic blockade with methylatropine did not alter the leukotriene hypotension. These data demonstrate the first dissociation of TRH and naloxone in experimental shock and suggest that the beneficial effects of TRH in this model result from central interactions which are not mediated by endogenous opioids. The findings further provide a potential link between the physiological (that is, cardiovascular) effects of a peptide (TRH) and those of a leukotriene; this may have implications with regard to the pathophysiology and therapy of anaphylaxis.

Animals↗
PubMed1983

Dermorphin: cardiovascular and sympathetic modulation in the anteroventral hypothalamus of conscious rats.

Cardiovascular and sympathetic responses to hypothalamic injections of dermorphin were studied in conscious rats. Microinjections of 10 pmol of dermorphin into the nucleus preopticus medialis (POM) elicited tachycardia without changing the mean blood pressure (MBP). A higher dose of dermorphin (100 pmol) caused prolonged tachycardia, and an increase in MBP. The pressor/tachycardic period following injection of 100 pmol dermorphin was accompanied by increased levels of plasma norepinephrine and epinephrine. These data suggest that the POM region is an important site for sympathetic activation and pressor/tachycardic effects of dermorphin.

Animals↗
PubMed1983

Leukotriene D4-induced hypotension is reversed by thyrotropin-releasing hormone.

Injection of leukotriene D4 (LTD4, 20 micrograms/kg, i.a.) to conscious spontaneous hypertensive (SHR) rats produces a short-lasting pressor and tachycardic response followed by prolonged hypotension and bradycardia. Plasma norepinephrine and epinephrine were elevated at the peak pressor/tachycardic phase as well as at the hypotensive phase. Injection of thyrotropin-releasing hormone (TRH, 2 or 5 mg/kg) at the peak of the LTD4-induced hypotension resulted in prompt reversal of the hypotension and bradycardia in a dose-related manner. Naloxone (5 mg/kg) had no effect on blood pressure and heart rate of LTD4-treated SHR rats. Pretreatment with TRH (5 mg/kg) did not prevent the depressor effect of LTD4, but attenuated the bradycardic effect of this leukotriene. In addition, TRH had no effect on LTD4-induced hypotension in the pithed SHR rat. These results suggest that TRH might exert beneficial effects in hypotensive states mediated by leukotrienes or other mediators of anaphylactic reactions.

Animals↗
PubMed1983

Thyrotropin-releasing hormone reverses the hypotension and bradycardia produced by leukotriene D4 in unanesthetized guinea pigs.

We have utilized an unanesthetized guinea pig model to study the cardiovascular effects of leukotriene D4 (LTD4), a compound implicated in slow reacting substance of anaphylaxis (SRS-A). Intravenous (IV) administration of LTD4 at 5 micrograms/kg produced profound hypotension, bradycardia, hypoxia and acidosis. The hypotension and bradycardia were rapidly and completely reversed by IV thyrotropin-releasing hormone (TRH) at a dose of 2 mg/kg. In contrast, TRH treatment had no effect on the hypoxia or acidosis induced by LTD4. These data provide a potential physiological link between two distinct classes of endogenous substances and may have implications for the therapy of anaphylactic shock.

Animals↗
PubMed1983

Hypothalamic regulation of the cardiovascular and respiratory systems: role of specific opiate receptors.

Experiments were designed to evaluate the role of mu and delta opiate receptors in central cardiovascular control in the hypothalamic nucleus preopticus medialis of rats anaesthetized with pentobarbitone. The highly selective mu opiate receptor agonist D-Ala2-MePhe4-Gly5-ol-enkephalin was extremely potent in eliciting hypotension and bradypnoea; tachycardia was elicited by a low dose (0.064 nmol), but not by higher doses (0.64-6.4 nmol). Other selective mu receptor agonists (morphine sulphate, morphiceptin) caused tachycardia at lower doses (0.64, 6.4 nmol), hypotension and bradypnoea after the highest dose (64 nmol). The relatively selective delta receptor agonist D-Ala2-D-Leu5-enkephalin caused profound bradypnoea and hypotension at the high dose (64 nmol), tachycardia after the lowest dose (0.64 nmol), but bradycardia was found during the hypotension induced by the high dose (64 nmol). All of the opiate/opioid effects were reversed by naloxone (0.5 mg kg-1, i.v.). It is concluded that mu receptors may mediate the cardiovascular and respiratory effects of opiates and opioid peptides in the nucleus preopticus medialis of the rat.

Animals↗
PubMed1983

Mu-receptors mediate opioid cardiovascular effects at anterior hypothalamic sites through sympatho-adrenomedullary and parasympathetic pathways.

Intracerebroventricular injections of selective opioid agonists were used to investigate the role of opiate receptor subtypes in cardiovascular function in awake rats. The mu-agonist (D-Ala2,MePhe4,Gly5-ol)enkephalin (1 nmol) caused a prolonged increase in blood pressure and an initial decrease followed by a delayed increase in heart rate. These effects were antagonized by the selective mu-antagonist beta-funaltrexamine. A selective delta-agonist (dimeric tetrapeptide enkephalin) was devoid of cardiovascular effects at 10 nmol, whereas a benzomorphan kappa-agonist MRZ caused a pressor response which was not antagonized by beta-funaltrexamine. The mechanisms by which opioids elicit cardiovascular effects were analyzed in detail by using microinjections into the anterior hypothalamic area. Low doses of enkephalin produced increases in heart rate and blood pressure. Associated elevations of plasma norepinephrine and epinephrine, but not vasopressin, suggested a stimulation of sympatho-adrenomedullary pathways. Higher doses caused increases in blood pressure but decreases in heart rate. Peripheral vagal blockade with atropine methyl nitrate caused a large sudden rise in heart rate, indicating that an increased vagal outflow counteracted the sympathetic activation. Adrenal demedullated rats displayed no tachycardia after anterior hypothalamic injection of low doses of enkephalin, whereas high dose caused pronounced bradycardia. Additional treatment of demedullated rats with the sympathetic blocker bretylium led to severe hypotension in addition to bradycardia. These data provide evidence that mu-opiate receptors primarily mediate cardiovascular effects of opiates in awake rats. At low doses, a sympathetic adrenomedullary activation occurs, whereas higher doses additionally activate parasympathetic efferents, both possibly from anterior hypothalamic sites.

Adrenal Medulla↗
PubMed1983

Effects of chronic arachidonate on blood pressure of spontaneously hypertensive rats.

Three weeks of treatment with arachidonic acid (250 mg/kg/day, s.c.) produced an antihypertensive effect in 16 week-old spontaneously hypertensive rats (SHR) as compared with vehicle treated rats. Indomethacin (4 mg/kg, s.c. B.I.D.), given concurrently with arachidonate, abolished the antihypertensive effect. Plasma catecholamines were not altered by the arachidonate treatment, but blood pressure increments after spinal cord stimulation or after intravenous administration of norepinephrine and angiotensin II in the pithed rat were diminished. Increments in plasma catecholamines in response to spinal cord stimulation were similar in both groups of pithed rats. These data demonstrate the antihypertensive effect of arachidonic acid in SHR with established hypertension. This beneficial effect seems to be mediated through cyclooxygenase metabolites, and might be related to reduced responsiveness of peripheral blood vessels to pressor stimuli.

Angiotensin II↗
PubMed1983

Cardiovascular and respiratory effects of mu-, delta- and kappa-opiate agonists microinjected into the anterior hypothalamic brain area of awake rats.

Relatively selective mu-, delta- and kappa-opiate agonists were microinjected into anterior hypothalamic and septal brain regions of the unanesthetized rat in order to investigate the potential role of specific opiate receptors in central cardiovascular regulation. Low doses (0.2-3 nmol) of both [D-Ala2,MePhe4,Gly-(ol)5] enkephalin (DAGO, mu-agonist) and [D-Ala2,D-Leu5]enkephalin (DADL, delta-agonist) caused dose-dependent increases in blood pressure and heart rate which were naloxone reversible. Higher doses (7.5-30 nmol) of DAGO and DADL produced pressor responses but had little effect on heart rate. The kappa-agonist MR 2034 had no effect on cardiovascular parameters at these doses. DAGO but not MR 2034 also depressed respiration at the higher doses resulting in hypoxia, hypercapnia and acidosis while DADL only slightly depressed respiration. DAGO was approximately 10-fold more potent than DADL in eliciting cardiovascular and respiratory responses. These findings implicate mu-receptors in mediating the cardiovascular and respiratory effects of opiates at anterior hypothalamic sites.

Animals↗
PubMed1983

Adrenalectomy blocks pressor responses to naloxone in endotoxic shock: evidence for sympathomedullary involvement.

The effects of naloxone on endotoxic hypotension in adrenalectomized and selectively adrenal demedullated rats were evaluated. In sham-operated rats, naloxone administered intracerebroventricularly (ICV) and intravenously (IV) produced an elevation of arterial pressure in this conscious rat model of endotoxemia. By contrast, both adrenalectomy and selective adrenal demedullation (wherein cortical function remained) not only enhanced the sensitivity to endotoxin-induced hypotension at least 10- to 15-fold, but also completely prevented the pressor response to ICV or IV naloxone. These results indicate that 1) adrenal enkephalins are probably not the endogenous opiates responsible for shock hypotension since their removal enhances shock susceptibility; 2) pituitary-derived endorphins in the circulation also appear to be uninvolved since naloxone fails to reverse shock hypotension despite reported elevations of circulating beta-endorphin in adrenalectomized rats; 3) since evidence indicates that naloxone acts centrally in intact endotoxemic rats and fails to do so following adrenal demedullation, we suggest that endotoxic shock results in an endogenous opiate inhibition of central autonomic sites regulating sympatho-medullary outflow. Naloxone, by reversing these actions, may result in the increased release of pressor substances from the adrenal medulla.

Adrenal Medulla↗
PubMed1983

Central autonomic effects of dermorphin in conscious rats.

Central cardiovascular and respiratory effects of dermorphin were studied in conscious rats. Intracerebroventricular administration (0.1 or 1 nM) of dermorphin increased the systolic and diastolic blood pressure whereas a high dose (50 nM) decreased blood pressure. Dermorphin at 1 nM increased respiratory rate but caused hypoxia, acidosis and hypercapnia; at 50 nM, respiratory rate was suppressed. Both of these doses produced catalepsy. Stimulation of the sympathoadrenomedullary axis at the pressor period elicited by 1 nM dermorphin was evident by high circulating levels of epinephrine and norepinephrine. N-methyl-atropine reversed the severe bradycardia induced by dermorphin and completely prevented this phenomenon if given as pretreatment. Neither blood pressure nor respiratory depression was altered by the muscarinic blocker. Naloxone (1 mg/kg) reversed the respiratory, cardiovascular and sympathetic effects of dermorphin as well as the catalepsy. These data show that dermorphin has central autonomic effects which are naloxone reversible and mediated by both sympathetic and parasympathetic pathways.

Animals↗
PubMed1982

Distribution of immunoreactive dynorphin in discrete brain nuclei; comparison with vasopressin.

The distribution of the opioid peptide, dynorphin, has been studied in discrete, microdissected hypothalamic nuclei, and compared with the distribution of vasopressin. Both peptides were found in relatively high concentration in the supraoptic and paraventricular nuclei. However, dynorphin-like immunoreactivity (DYN-LI) was much more widely distributed in the hypothalamus than vasopressin-like immunoreactivity, with highest concentrations in the anterior hypothalamic and ventromedial nuclei. DYN-LI was also observed in some extra-hypothalamic structures; concentrations which were comparable to the highest levels in the hypothalamus were found in the tractus diagonalis and the nucleus interstitialis stria terminalis. Among the three brainstem nuclei examined, DYN-LI levels were highest in the sensory nucleus of the trigeminal nerve.

Animals↗
PubMed1982

Catecholamines and vasopressin in hindbrain nuclei of hypertension prone and resistant rats.

Norepinephrine and epinephrine concentrations in the caudal and rostral part of the nucleus tractus solitarii (NTS) and in locus coeruleus (LC) of Sabra hypertension prone (SBH) rats are 2-4-fold higher than in the parent Sabra (SB) strain; SB rats have higher concentrations than the Sabra hypertension resistant (SBN) rats. Dopamine concentrations were higher in SBH as compared to SB and SBN rats only in the caudal NTS. Vasopressin concentrations in the NTS of SBH were 3-fold higher than the levels found in SB or SBN rats. These data suggest that catecholamines and vasopressin in specific brainstem nuclei are involved in either the pathogenesis or central response to hypertension in SBH rats.

Animals↗
PubMed1982

Hypothalamic sites for cardiovascular and sympathetic modulation by prostaglandin E2.

Prostaglandin E2 (PGE2, 0.5 - 5 nmol/kg) injected into the lateral cerebral ventricle of the rat increased the systemic blood pressure and heart rate in a dose dependent manner. These effects were accompanied by increases in plasma norepinephrine and epinephrine concentration. Injection of low dose of prostaglandin E2 into discrete hypothalamic nuclei induced a marked increase in heart rate, a moderate increase in the arterial blood pressure and a significant elevation of plasma norepinephrine level. This study suggests a possible central role for PGE2 in modulation of cardiovascular dynamics and sympathetic nervous activity.

Animals↗