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Biomedical subjects

G Feuerstein

Publications and source records attributed to G Feuerstein.

At least 199 records · Page 11Linked to original sources
PubMed1985

Effects of calcium entry blockers on coronary constriction and myocardial ischemia due to leukotriene D4.

Recent studies show that leukotrienes (LTs) produce profound coronary artery constriction. Although calcium entry blockers are commonly used to remedy coronary vasospasm, their capacity to interfere with LT-mediated coronary constriction is unknown. Therefore, we compared effects of intracoronary LTD4 before and during treatment with calcium entry blockers in the in situ, blood-perfused hearts of domestic pigs. Intravenous administration of verapamil (0.1-1.6 mg/kg), nifedipine (10 or 100 micrograms/kg) or diltiazem (0.6-2.0 mg/kg) sufficient to increase base-line coronary blood flow (CBF) and decrease mean arterial pressure did not change decrement in CBF after LTD4. Infusion of verapamil (0.01-0.04 mg/min) into the left anterior descending coronary artery raised pre-LTD4 CBF almost 2-fold without alteration in mean arterial pressure, heart rate or left ventricular end-diastolic pressure. Intracoronary boluses of LTD4 (0.3, 1.0 and 3.0 micrograms) during verapamil infusion into the same vessel caused dose-dependent decreases in CBF identical to those observed when LTD4 was injected during control infusion. ECGs showed myocardial ischemia during severe flow reduction after high dose intracoronary LTD4 (3.0 or 10.0 micrograms). When the same LTD4 doses were injected during intracoronary verapamil, electrocardiographic changes did not occur despite similar decreases in CBF. The capacity of verapamil to prevent LTD4-induced ischemia may be caused by higher residual CBF after LTD4 even though the magnitude of LTD4-induced CBF decrement was unaltered. LTD4-induced coronary constriction seems to be mediated by a mechanism unrelated to calcium entry channels blocked by verapamil, nifedipine or diltiazem.

Animals↗
PubMed1984

Simultaneous changes of catecholamines and of Leu-enkephalin-like immunoreactivity in plasma and cerebrospinal fluid of cats undergoing acute hemorrhage.

Cats, anesthetized with sodium pentobarbitone, underwent acute hemorrhagic shock by withdrawal of 15 ml blood/kg of body weight. The cerebral ventricular system was perfused with artificial cerebrospinal fluid (CSF). Blood and CSF samples were collected during 2 h, for the analysis of catecholamines (CA) and Leu-enkephalin-like immunoreactivity (LE-ir). The fall of blood pressure immediately after hemorrhage was accompanied by a rise of LE-ir in the CSF and by a decrease of norepinephrine and dopamine below their control values. About half an hour later, the LE-ir returned to its initial low level, while the CA were now markedly elevated. A similar opposite behavior of peptides and CA was observed during subsequent sampling periods, although blood pressure remained constant. These experiments demonstrate an inverse relationship of LE-ir and CA in the CSF, after acute hemorrhagic shock.

Animals↗
PubMed1984

Differential changes in substance P and somatostatin in brain nuclei of rats exposed to hemorrhagic shock.

Concentrations of immunoreactive substance P ( SPir ) and immunoreactive somatostatin ( SSir ) were determined in discrete brain nuclei of normal rats and rats exposed to acute hypovolemic hypotension (8 ml/300 g body weight). SPir in the hypothalamic paraventricular nucleus (PVN) and the caudal and rostral parts of the nucleus of the tractus solitarius (NTS) were significantly reduced 2 h after hemorrhage, but no changes were found in any of the brain nuclei when examined 5 min after the same bleeding. SSir in the NTS and nucleus ambiguus (NA) were reduced by 50-60% 2 h after the hemorrhage, as compared either to intact rats or rats examined 5 min after bleeding. In the forebrain, significantly lower concentrations of SSir were found in the nucleus supraopticus at both 5 min and 2 h after shock and in the PVN of rats 2 h after shock. These data suggest a role for SPir and SSir in central adaptation to hypovolemic hypotension and further indicate that functions regulated by these neuropeptides might be substantially affected by shock states.

Animals↗
PubMed1984

An increase in opiate receptor-sites is associated with enhanced cardiovascular depressant, but not respiratory depressant action of morphine.

Rats were treated for 4 weeks with a constant infusion of 2 mg/kg/h of the opiate antagonist naloxone. This treatment increased mu-, delta- and kappa-binding sites by 60-180% in several brain regions, suggesting effective blockade of the 3 types of opiate sites. The significance of changes in opiate binding sites for opiate receptor mediated physiological responses were examined using cardiovascular and respiratory responses to morphine (assessed after elimination of naloxone) as physiological parameters. Chronically naloxone-treated rats showed no alteration in respiratory responses to morphine, whereas there was a marked supersensitivity to depressor and bradycardic effects and a loss of pressor and tachycardic effects of morphine. These data are the first indication that cardiovascular effects of opiates vary with changes in central opiate receptor levels. Our observations, moreover, show that there are complex relationships between receptor number and receptor-mediated effects of opiates.

Animals↗
PubMed1984

Peripheral pressor effects of sympathetic stimulation, noradrenaline, angiotensin II and vasopressin in Brattleboro rats.

The following study was designed to test the hypothesis that peripheral blood vessels of vasopressin deficient (Di/Di) rats are less responsive to pressor substances than normal rats. To address this question, pithed Di/Di and normal Long-Evans rats (LE) were exposed to intravenous injections of arginine-vasopressin, angiotensin II and noradrenaline. In addition, blood pressure increments and noradrenaline release in response to spinal cord stimulation in pithed Di/Di and LE rats were studied. The results show no abnormalities in peripheral vascular sensitivity to any of the pressor substances administered, nor was there any change in blood pressure and sympatho-adrenomedullary response to graded stimulation of the sympathetic outflow from the spinal cord. This study suggests that the failure of vasopressin deficient rats to recover from acute hemorrhage is not due to hyporesponsiveness of the peripheral vasculature to pressor agents but, rather, to the deficiency in the direct pressor effect of vasopressin.

Angiotensin II↗
PubMed1984

Selective cardiorespiratory effects mediated by mu opioid receptors in the nucleus ambiguus.

The respiratory and cardiovascular effects of the highly selective mu opioid agonist, D-Ala2, MePhe4, Gly- ol5 enkephalin ( DAGO ) and the relatively selective delta agonist, D-Leu5 enkephalin (DADL) were compared following injection (0.1 microliter) into the nucleus ambiguus (NA) of spontaneously-breathing and artificially-respired, pentobarbital-anesthetized rats. In non-ventilated animals, the opioids elicited dose-related (3 X 10(-11) -3 X 10(-9) M), naloxone-reversible depression of respiratory rate (RR) without altering the tidal volume. Mean arterial pressure (MAP) was unchanged at small doses and decreased at the largest dose; heart rate (HR) was unchanged. In artificially-respired animals, both peptides elicited dose-related, naloxone-reversible increases in mean arterial pressure and heart rate; DAGO was significantly more potent than DADL (P less than 0.01). Given the relative potency and selectivity of the opioids tested, these findings are consistent with the conclusion that mu receptors may selectively mediate the respiratory and cardiovascular actions of opioids in an important brain stem cardiorespiratory center in the rat. Moreover, these data indicate the importance of respiratory effects on the cardiovascular activity of centrally administered opioids.

Animals↗
PubMed1984

Differential effect of fluorinated analogs of TRH on the cardiovascular system and prolactin release.

The effects of thyrotropin-releasing hormone (TRH) and the TRH-analogs, 4-fluoro-Im-TRH (4-F-TRH) and 2-trifluoromethyl-Im-TRH (2-TFM-TRH), on the cardiovascular system and prolactin (PRL) release were examined in conscious rats. TRH (2.8 or 28 nmol) injected into the anterior hypothalamus produced dose-dependent increments in blood pressure and heart rate; plasma PRL was increased twofold after the higher dose of TRH. 4-F-TRH had effects similar to those of TRH on both the cardiovascular and PRL response. In contrast, the 2-TFM-TRH was significantly less active than TRH or 4-F-TRH in eliciting tachycardia, yet was noticeably more potent in affecting PRL release. These data suggest that the receptors for TRH-induced PRL release may be different from TRH-receptors which mediate central cardiovascular responses.

Animals↗
PubMed1984

Cardiovascular effects of dynorphin A-(1-8), dynorphin A-(1-13) and dynorphin A-(1-17) microinjected into the preoptic medialis nucleus of the rat.

Multiple forms of Dynorphin A (Dyn A) are present in cardiovascular nuclei in the hypothalamus, along with kappa-opiate receptors. To study the potential role of Dyn A in cardiovascular regulation, various Dyn A species [Dyn A-(1-8; 1-13; 1-17)] were microinjected into the preoptic nucleus (POM) of the anesthetized rat. Dyn A-(1-17) was tenfold more potent than Dyn A-(1-13), and over 100-fold more potent than Dyn A-(1-8) in reducing systemic blood pressure. High doses of Dyn A-(1-17) (6 nmoles) produced shock with severe bradycardia and bradypnea. These data suggest that Dyn A may be an endogenous modulator of cardiorespiratory variables in the anteroventral hypothalamus, and demonstrate that the larger fragments of the peptide are more active in eliciting central cardiorespiratory activity in this region.

Animals↗
PubMed1984

Reversal of leukotriene D4 hypotension by thyrotropin-releasing hormone.

Thyrotropin-releasing hormone (TRH) reversed the hypotension produced by leukotriene D4 (LTD4) (5 micrograms/kg, i.v.) in conscious guinea pigs in a dose-dependent fashion at intravenous doses between 0.2 and 2.0 mg/kg. LTD4 hypotension was also reversed by the synthetic TRH analog MK771 (0.2 or 2 mg/kg, i.v.), suggesting a possible receptor-mediated mechanism. Since LTD4 has been implicated as a mediator of anaphylaxis, these results provide a basis for further evaluation of TRH and its analogs in the treatment of anaphylactic shock.

Animals↗
PubMed1984

Effect of platelet-activating factor on coronary circulation of the domestic pig.

The platelet-activating factor released by white blood cells and platelets has been shown to be 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC). To fully understand the cardiovascular actions of this substance, we examined the effects of AGEPC on coronary blood flow (CBF) and other hemodynamic parameters in anesthetized open-chest domestic pigs. Mean arterial blood pressure (MBP), electrocardiogram, heart rate (HR), left ventricular pressure, and CBF were continuously recorded. AGEPC was injected (bolus, 0.1 ml) into the left anterior descending coronary artery at increasing doses of 0.03-10 nmol. Intracoronary AGEPC produced biphasic changes in CBF: a dose-dependent increase in CBF (up to 50%) followed by a decrease (up to 92%) in CBF. The changes in CBF were not directly related to any systemic effect, although MBP was reduced consistently after a dose higher than 1 nmol of AGEPC. The increase in CBF produced by AGEPC was not affected by pretreatment with indomethacin (6 mg/kg) or FPL 55712 (1 or 3 mg), an inhibitor of slow-reacting substance of anaphylaxis (SRS-A). The decrease in CBF produced by AGEPC was attenuated by FPL 55712 and blocked by indomethacin. These data suggest that AGEPC release from aggregating platelets might play a major role in modulating CBF and cardiac function in states involving platelet-coronary interaction.

Animals↗
PubMed1984

Anteroventral hypothalamus and hemorrhagic shock: cardiovascular and neuroendocrine responses.

The anteroventral third ventricle (AV3V) region was shown to be a site of central integration of sympathetic pressor pathways and central pressor and vasopressin (VP) release by angiotensin II (ANG II). Since the AV3V area seems to have an important role in the regulation of the three major pressor systems, we investigated the role of the AV3V in cardiovascular recovery after hemorrhage, a known stimulus for sympathetic, ANG II, and VP release. Conscious AV3V-lesioned (n = 19) and sham-operated rats (n = 14) underwent bleeding (40% of blood volume) through an arterial line. Mean blood pressure, heart rate, and plasma ANG II, VP, and catecholamines were monitored over 24 h. The exact site of lesion was determined by microscopic examination. The mean blood pressure and heart rate of both groups of rats were not different before or after hemorrhage. Plasma catecholamines, ANG II, and VP responses were also the same as were hematocrit and water consumption 24 h after the bleeding. Despite the lack of difference between control and lesioned animals with regard to cardiovascular, humoral, and neuroendocrine responses to hypovolemia, the AV3V-lesioned rats had a significantly higher early mortality rate. These data indicate that the AV3V may be an important region in recuperation and survival after hemorrhagic shock, but through mechanisms unrelated to activation of VP, renin-ANG II, or the sympathetic nervous system.

Angiotensin II↗
PubMed1984

Cardiovascular and sympathetic effects of leukotriene D4 in renovascular and spontaneously hypertensive rats.

Leukotriene D4 (LTD4), a constituent of slow-reacting substance of anaphylaxis (SRS-A), elicits a pressor response followed by prolonged hypotension in spontaneously hypertensive (SHR) but not in Wistar-Kyoto (WKY) rats. In order to investigate whether the depressor response to LTD4 in SHR rats is related to hypertension itself, we have studied the cardiovascular and sympathetic effects of LTD4 in 1-kidney, 1-clip hypertensive rats and 1-kidney, normotensive rats. In all groups of conscious rats, intra-arterial administration of LTD4 (0.2-20 micrograms/kg) caused dose-dependent pressor responses of similar degree except in WKY rats, which responded less. Only SHR rats developed a significant and progressive hypotension (-58 +/- 5 mm Hg) following pressor phase. In all but WKY rats, the response phase was attended by an increase in plasma levels of norepinephrine and epinephrine. Only SHR rats showed marked and persistent hemoconcentration following pressor effect. Thus, depressor response of SHR rats to systemic administration of LTD4 does not appear to be merely due to the magnitude of blood pressure elevation and may in part result from microcirculatory changes not present in other hypertensive rats.

Adrenal Medulla↗
PubMed1984

Kappa opioid receptors modulate cardiorespiratory function in hindbrain nuclei of rat.

The respiratory and cardiovascular effects of selective kappa opioid agonists were compared following microinjection (0.1 microliter) into the nucleus ambiguus (NA) and the nucleus tractus solitarius (NTS) regions of spontaneously breathing and artificially respired pentobarbital-anesthetized rats. In spontaneously breathing animals, the benzomorphan derivative MRZ 2549 (MRZ, 3 X 10(-11) to 16 X 10(-9) mol) elicited dose-related decreases of mean arterial pressure (MAP), heart rate (HR), and tidal volume (TV) following NA injection; bremazocine (BREM) decreased MAP, HR, and respiratory rate (RR). Following NTS injection, MRZ (3 X 10(-10) to 16 X 10(-9) mol) lowered MAP and TV, the highest dose also lowering HR and RR; BREM (3 X 10(-9) to 16 X 10(-9) mol) decreased MAP and HR. Naloxone (200 micrograms/kg, i.v.) reversed the respiratory effects of MRZ without consistently altering cardiovascular activity. In ventilated animals, NA injections of MRZ or BREM (3 X 10(-9) to 16 X 10(-9) mol) elicited a dose-related decrease of MAP without altering HR. These responses were not reversed by naloxone. The stereoisomer of BREM (+ BREM) was without effect at similar doses (3 X 10(-9) to 16 X 10(-9) mol). MRZ (16 X 10(-9) mol) elicited a naloxone-reversible tachycardia following NTS injection in ventilated animals; no other cardiovascular responses were observed following NTS administration of BREM (16 X 10(-9) mol) or lower doses of MRZ. Dynorphin (1-13) (6 X 10(-9) to 60 X 10(-9) mol) significantly lowered MAP without altering HR following NA microinjections in ventilated animals; the lower dose decreased MAP following NTS injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Hypotension produced by platelet-activating factor is reversed by thyrotropin-releasing hormone.

Platelet-activating factor (PAF), a vasoactive phospholipid implicated in anaphylactic reactions, causes severe hypotension in experimental animals that is highly resistant to pharmacological therapy. In the present studies, we showed that PAF (1 nmol/600 g body weight, IV) produced profound hypotension in unanesthetized guinea pigs that was promptly and completely reversed by thyrotropin-releasing hormone (TRH) (2 mg/kg, IV) or by the synthetic TRH analog MK771 (2 mg/kg, IV). TRH also reversed this hypotension when administered intracerebroventricularly (ICV) at a dose (0.02 mg/kg) that was systemically ineffective. The opiate receptor antagonist naloxone (5 mg/kg) was less effective than TRH in reversing the cardiovascular consequences of PAF administration. These data suggest that TRH reverses PAF-induced shock through central receptor-mediated mechanisms. This therapeutic action of TRH may partially account for the beneficial cardiovascular effects of this peptide in anaphylactic shock.

Animals↗
PubMed1984

Leukotriene D4 inhibits cardiovascular responses to sympathetic stimulation, angiotensin and vasopressin in the pithed spontaneously hypertensive rats.

We have previously shown that high doses of leukotriene D4 (LTD4) induces hypotension in conscious and in pithed spontaneously hypertensive rats. The present study was designed to determine whether the hypotensive effect of LTD4 in spontaneously hypertensive rats is due to reduced sensitivity of peripheral blood vessels to pressor stimuli and/or reduced responsiveness of the sympatho-adrenomedullary system. To test these possibilities we examined the effect of spinal cord stimulation, vasopressin, norepinephrine and angiotensin II on blood pressure, heart rate and plasma catecholamines of pithed spontaneously hypertensive rats, before and after treatment with LTD4 (20 micrograms/kg i.v.), a dose which produces hypotension in conscious and pithed rats. LTD4 suppressed the pressor responses to spinal cord stimulation (50 V, 1 msec, for 1 min) at 0.3 and 3.0 Hz by 64% (P less than .001) and 71% (P less than .001), respectively, and the pressor and cardiac accelerating effects of systemic injections of norepinephrine. Plasma norepinephrine response to spinal cord stimulation at 3.0 Hz was significantly (P less than .05) reduced after administration of LTD4. The evoked release of epinephrine from the adrenal medulla was enhanced (+139%, P less than .05) by LTD4, but the tachycardia was blocked. The pressor responses to 0.1 and 1.0 microgram/kg of angiotensin II were blocked by 73% (P less than .05) and 70% (P less than .01), respectively. The pressor effects produced by vasopressin (0.03 and 0.1 microgram/kg) were also attenuated (by 83 and 80%, respectively) after LTD4 administration. The depressor effect of sodium nitroprusside (0.01-0.1 mg/kg) was also attenuated by LTD4. These data suggest that LTD4-induced hypotension involves severe interference with vascular smooth muscle responsiveness to all pressor agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗