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Biomedical subjects

A H Hassen

Publications and source records attributed to A H Hassen.

17 recordsLinked to original sources
PubMed2001

Inhibitors of bradykinin-inactivating enzymes decrease myocardial ischemia/reperfusion injury following 3 and 7 days of reperfusion.

Inhibitors of bradykinin (BK)-inactivating enzymes protect from myocardial ischemia/reperfusion injury after short periods of reperfusion. However, protection after 2 to 3 h of reperfusion does not mean that myocardium remains viable for an extended time. Therefore, we examined the effects of inhibitors of angiotensin-converting enzyme (ramiprilat), EP24.11 (cFP-F-pAB), and EP24.15 (cFP-AAF-pAB) in a chronic model of myocardial ischemia/reperfusion injury. A left descending coronary artery was occluded for 30 min in anesthetized rabbits. Saline, ramiprilat, or endopeptidase inhibitors were given after 27 min of occlusion. The BK(2) receptor antagonist HOE140 was administered in certain experiments. After ischemia, the occlusion was released, and the animal allowed to recover for 3 or 7 days. Surgery was then repeated, and the heart removed for determination of infarct size. In separate experiments, the heart was removed after 2 h of reperfusion for determination of BK tissue levels. Ramiprilat and endopeptidase inhibitors reduced infarct size at 3 and 7 days. Combining inhibitors further reduced infarct size after 3 days. The protective effect of the endopeptidase inhibitors was blocked by HOE140. Infarct sizes at 7 days were larger than at 3 days. The additive effect of multiple inhibitors was absent at 7 days. Ramiprilat and cFP-F-pAB significantly increased tissue BK levels. We conclude that inhibition of BK-inactivating enzymes protects endogenous BK from degradation and provides long-lasting protection from myocardial ischemia/reperfusion injury. A single treatment at the time of reperfusion does not prevent extension of the infarction between 3 and 7 days.

4-Aminobenzoic Acid↗
PubMed1996

Endopeptidase inhibitors decrease myocardial ischemia/reperfusion injury in an in vivo rabbit model.

Periods of ischemia followed by reperfusion of the ischemic tissue are associated with myocardial damage and ventricular arrhythmia. Angiotensin converting enzyme inhibitors limit the occurrence of these arrhythmias. The protective effects of angiotensin converting enzyme inhibitors may be due to inhibition of bradykinin (BK) degradation, rather than inhibition of angiotensin II formation. Other enzymes which catabolize BK include the endopeptidases EP24.11 and EP24.15. The purpose of this study was to determine if inhibitors of EP24.11 and EP24.15 decrease ischemia/reperfusion injury and if this protection is mediated by BK receptors. Rabbits were anesthetized and prepared for recording of cardiovascular parameters. The chest was opened and a left ventricular artery occluded for 30 min, followed by a 2-hr reperfusion period. Infarct size was determined using triphenyl tetrazolium chloride staining immediately after reperfusion. The enzyme inhibitors, ramiprilat, N-[1-(R,S)-carboxy-3-phenylpropyl]-Phe-pAB, and N[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-pAb, singly and in combinations were administered 3 min before reperfusion. Compared to saline (32.1 +/- 2.1), ramiprilat (18.3 +/- 2.8) and the EP inhibitors (14.4 +/- 1.4 for the combination) significantly decreased infarct size, with the greatest decrease occurring when all three inhibitors were combined (10.6 +/- 1.5). The protective effect of the EP inhibitors was blocked by the BK2 receptor antagonist, HOE 140 (30.1 +/- 2.6). Enzyme assays demonstrated EP24.11 and EP24.15 in the rabbit heart. We conclude that the EP inhibitors decreased ischemia/reperfusion injury by protecting BK from metabolism and that a combination of inhibitors provides superior protection to that given by a single agent.

Aminobenzoates↗
PubMed1990

The effect of tinnitus on ABR latencies.

Comparisons were made of the ABR latencies of tinnitus (T) and nontinnitus (NT) patient groups balanced for age and gender and matched for acoustic reflex threshold (ART)s, 1000 to 4000 Hz and 4000 Hz auditory thresholds, and normal hearing. In the ART match, prolongations of wave I [t(94) = 4.42, p less than 0.001], wave III [t(94) = 2.72, p less than 0.01], and wave V [t(94) = 3.32, p less than 0.01] and the III-V interval [t(94) = 2.48, p less than 0.02) were seen in T subjects. Wave I in 1 to 4 kHz matched [t(62) = 3.13, p less than 0.005] and normal-hearing subjects [t(30) = 2.58, p less than 0.01] was prolonged in T females. The utility of using wave I as a diagnostic indicator for tinnitus in females is discussed.

Adult↗
PubMed1989

Decapitation increases plasma sodium and potassium in the rat.

Sodium, potassium, and osmolality were measured in plasma obtained from conscious and decapitated rats. The sodium and potassium content of plasma derived from blood taken from decapitated rats via arterial cannulae or free-flowing trunk blood was significantly greater than that in conscious animals or animals killed by an overdose of pentobarbital. Plasma osmolality was not different. Hemoglobin was present in the plasma of decapitated rats, suggesting hemolysis. Hemolysis and subsequent release of intracellular potassium may be the cause of the elevated plasma potassium. The cause of the elevated sodium is unclear. This study points out the importance of considering the method of obtaining blood in determinations of plasma levels of biologic substances.

Animals↗
PubMed1988

Selective autonomic modulation by mu- and kappa-opioid receptors in the hindbrain.

In the Nucleus Ambiguus (NA) mu-receptors increased mean arterial pressure (MAP) and heart rate (HR) and kappa-receptors decreased MAP without altering HR. Mu-receptors in the Dorsal Motor Nucleus of the Vagus (DMV) increased MAP without changing HR whereas kappa-receptors in the DMV decreased HR without changing MAP. The pathways which mediate these responses were studied in anesthetized, artificially ventilated rats. Transection of the spinal cord at the C1 segment blocked the pressor response and tachycardia elicited following microinjection of a mu-agonist into the NA. The depressor response elicited by a kappa-agonist was not changed. Complete attenuation of the kappa response was produced by combining spinal transection with bilateral vagotomy. The pressor response produced following microinjection of a mu-agonist into the DMV was attenuated by pretreatment with the sympathetic blocking drug guanethidine. Atropine methyl nitrate pretreatment blocked the bradycardia elicited by a kappa-agonist and revealed an underlying tachycardic response to the mu-agonist. These data show that mu- and kappa-receptors in the NA and DMV modulate cardiovascular activity by selective modulation of sympathetic and parasympathetic pathways.

Animals↗
PubMed1987

mu-Opioid receptors in NTS elicit pressor responses via sympathetic pathways.

We have evaluated the relative contributions of the sympathetic and parasympathetic nervous systems to the increased mean arterial pressure (MAP) and heart rate (HR) elicited by the selective mu-agonist D-Ala2, MePhe4, Gly-ol5 enkephalin (DAGO) following microinjection (100 nl) into the nucleus of tractus solitarius (NTS) of anesthetized, artificially ventilated Sprague-Dawley rats. The effects of anesthesia and central opioid-receptor activation on baroreflex function were also examined. All cardiovascular responses elicited by DAGO were eliminated by complete C1 spinal transection. Pretreatment with the alpha-adrenergic antagonist phentolamine attenuated the increase in MAP, but not the tachycardia; the beta-blocker propranolol abolished the tachycardia but not the pressor response to DAGO. Adrenalectomy, vagotomy, or pretreatment with atropine methyl nitrate were all without effect. Baroreflexes were attenuated in animals anesthetized with pentobarbital sodium, but were present in urethan-anesthetized rats. DAGO attenuated the increases in MAP and HR elicited following carotid occlusion, but not the bradycardia elicited by a phenylephrine-induced pressor response. These data indicate that mu-receptors in the NTS elicit cardiovascular responses that are mediated by increased sympathetic nerve activity, and accompanied by selective attenuation of baroreflex function.

Adrenalectomy↗
PubMed1986

Response of rat pituitary anterior lobe prodynorphin products to changes in gonadal steroid environment.

The total content of rat pituitary anterior lobe (AL) immunoreactive (ir) dynorphin A (ir-Dyn A) and ir-dynorphin B (Dyn B) increased in male rats between 15 and 58 days of age, but there was little alteration in the concentration of ir-Dyn A or B expressed relative to protein content. Adult rats (90 days of age) had lower concentrations of these peptide immunoreactivities in the AL. Castration of 58-day-old male rats produced a testosterone-reversible loss of ir-Dyn A and B by 50-60% 3 days after surgery. Thereafter, the levels of these peptides gradually increased to 2.5 times the levels found in control animals at 1 month after castration. These effects of castration on AL dynorphin were not seen in 15-day-old rats and were much less marked in adults. Similar changes were seen in the levels of other prodynorphin products, alpha- and beta-neo-endorphin (ir-alpha-nEnd and ir-beta-nEnd), and ir-[Leu5]enkephalin (ir-LE). Administration of testosterone (100 micrograms/100 g BW) to castrated rats for 2 days largely prevented the drop in the levels of AL ir-Dyn A and B. Ovariectomy produced an increase in the levels of ir-Dyn A, Dyn B, alpha-nEnd, beta-nEnd, and LE 2 weeks after surgery, but, in contrast to castration, no significant decrease was seen 3 days after ovariectomy. These changes in AL content of dynorphin-related peptides after castration or ovariectomy directly reflect those previously reported for AL content of LH. The mechanisms regulating storage (and perhaps secretion) of AL peptides derived from prodynorphin may be similar to those regulating storage and secretion of LH and FSH in rat AL. AL ir-LE could potentially arise from proenkephalin A or prodynorphin (proenkephalin B). Ir-LE levels in AL were approximately 10 times higher than the levels of ir-[Met5]-enkephalinyl-Arg-Gly-Leu (ME-RGL) in male rat AL, and changes in ir-LE content after castration were very similar to those observed in other prodynorphin-derived peptides, but different from the effects of castration on ir-ME-RGL. It is possible that prodynorphin is a major source of AL ir-LE.

Animals↗
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

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↗
PubMed1982

Delta versus mu receptors: cardiovascular and respiratory effects of opiate agonists microinjected into nucleus tractus solitarius of cats.

The cardiovascular and respiratory responses to relatively specific mu or delta agonists microinjected (0.5 microliter/kg) into the region of the nucleus of tractus solitarius (NTS) were examined in anesthetized cats. Blood pressure, heart rate, and respiratory rate were monitored for 30 min after the microinjection of opioid compounds or saline vehicle. The delta agonist, (D-Ala2,D-Leu5)-enkephalin (10-100 nmol/kg) elicited dose-dependent decreases in blood pressure, heart rate, and respiratory rate which were naloxone reversible. In contrast the mu agonists, morphine (10-54 nmol/kg) and morphiceptin (100-320 nmol/kg) had no effect on blood pressure or respiratory rate; yet, naloxone elicited pressor responses in animals pretreated with these mu agonists. A receptor-binding assay demonstrated a predominance of mu sites in the NTS. These data show that the delta opiate agonist is more effective than mu agonists in modifying cardiovascular variables in the NTS; we suggest caution in relating specific cardiovascular function to receptor subtypes defined by binding assays.

Animals↗
PubMed1975

Bilateral effects of vestibular nerve stimulation on activity in the lumbar spinal cord.

These experiments were designed to study the effects of vestibular nerve stimulation on the activity of hindlimb motoneuron pools. Two techniques were used to stimulate the vestibular nerves of precollicularly decerebrated cats. In one set of experiments the individual semicircular canals were stimulated via bipolar electrodes placed near the canal nerves. In the second series of experiments the whole vestibular nerve was stimulated with an electrode placed on the intradural nerve. Activity in the hindlimb motoneuron pools was ascertained by evoking monosynaptic reflexes in the various hindlimb nerves. Stimulation of the individual semicircular canals produced response patterns that varied with both the vestibular branch being stimulated and the hindlimb nerve being conditioned. Intradural stimulation of the vestibular nerve, on the other hand, evoked similar response patterns in the antagonist ankle flexor and extensor nerves. The most common pattern consisted of facilitation followed by a period of inhibition. Lesions of descending fiber tracts produced results which suggest the presence of a diffuse pathway, involving the recitular formation, which mediates the observed responses. It is suggested that the biphasic response pattern is analogous to the startle response and the function of the responses is discussed in that context.

Animals↗
PubMedDate not supplied

Cardiovascular responses to opioid agonists injected into the nucleus of tractus solitarius of anesthetized cats.

It has been proposed that various opiate receptor subtypes mediate different cardiovascular responses to centrally administered opioids. We evaluated this hypothesis in chloralose-urethane anesthetized cats by monitoring the cardiovascular and respiratory responses to relative mu [morphine, morphiceptin, D-Ala2, MePhe4, Gly-ol5 enkephalin (DAGO)] and delta [D-Ala2, D-Leu5enkephalin (DADL)] agonists microinjected (0.5 ul/kg) into the caudal region of the Nucleus of Tractus Solitarius (NTS). Dynorphin (1-13), an endogenous opioid which exhibits selective affinity towards the kappa receptor, was also tested. Dynorphin at a dose of 50 nMol/kg did not alter cardiovascular or respiratory variables. Morphine (10-54 nMol/kg) and DAGO (50 nMol/kg) had no effect on blood pressure, heart rate or respiratory rate; morphiceptin (100-320 nMol/kg) caused tachycardia only at the highest dose. DADL (10-100 nMol/kg) elicited a dose-dependent depression of blood pressure. High doses of DADL depressed heart rate and respiratory rate. The depressor effects of DADL were reversed by low doses of naloxone (0.1 mg/kg). This dose of naloxone also elicited pressor responses in cats treated with the other opioids and reversed the morphiceptin-induced tachycardia. These data indicate that opioid agonists differ with regard to their cardiovascular and respiratory effects following microinjection into the NTS of anesthetized cats, with the delta agonist DADL showing greatest activity.

Animals↗
PubMedDate not supplied

mu Receptors and opioid cardiovascular effects in the NTS of rat.

In order to assess the potential role of mu (mu) and delta (delta) opiate receptors in the central regulation of the cardiovascular and respiratory systems, the cardiovascular and respiratory effects of the relatively selective mu-opioid agonist D-Ala2, MePhe4, Gly-ol5 enkephalin (DAGO) and relatively selective delta-agonist D-Ala2-D-Leu5 enkephalin (DADL) were compared following microinjection of these compounds into the nucleus tractus solitarius of pentobarbital-anesthetized rats. Both opioid agonists produced dose dependent increases in systolic and diastolic blood pressure as well as heart rate; but DAGO was nearly ten times more potent in eliciting these changes. Respiratory rate was increased by DADL and by lower doses of DAGO, but was depressed by higher doses of DAGO. Tidal volume was depressed by both peptides. These data support the concept that the cardiovascular pressor responses and tachycardia as well as the respiratory effects of opioids in the rat NTS are mediated by mu receptors.

Animals↗
PubMedDate not supplied

TRH: cardiovascular and sympathetic modulation in brain nuclei of the rat.

The cardiovascular and sympathetic effects of TRH in discrete cardiovascular-related brain nuclei were studied. Microinjections of TRH were made into the nucleus preopticus medialis (POM) of conscious rats and the nucleus tractus solitarius (NTS) of pentobarbitone-anesthetized, artificially respired rats. POM injections (1 microliter, 0.8-80 nM) elicited dose dependent pressor and tachycardic responses which were accompanied by increased levels of norepinephrine (NE) and epinephrine (EPI) in the plasma. These pressor/tachycardic effects of TRH were also elicited in adrenal demedullated (ADM-x) rats, but completely abolished in ADM-x rats pretreated with bretylium (30 mg/kg, IA). NTS injections (0.1 microliter, 30 and 150 nM) had a short depressor effect on blood pressure (BP) and a delayed increase in heart rate (HR). From these findings we suggest that the POM, a central nucleus in the AV3V region, may be an important forebrain site for autonomic regulation by TRH, mediated through the sympathetic nervous system.

Adrenal Medulla↗
PubMedDate not supplied

Differential cardiovascular effects mediated by mu and kappa opiate receptors in hindbrain nuclei.

To further investigate the role of opioid peptides and specific opiate receptor subtypes in central cardiovascular regulation by hindbrain nuclei, mu (D-Ala2,MePhe4,Gly-ol5 enkephalin, DAGO), delta (D-Ala2,D-Leu5 enkephalin, DADL) or kappa (MRZ 2549) agonists were microinjected into hindbrain nuclei of spontaneously or artificially respired, pentobarbital-anesthetized rats. In the nucleus tractus solitarius (NTS), DAGO and DADL (0.3 nmol) elicited pressor responses and tachycardia. MRZ (3.0-16 nmol) depressed blood pressure in spontaneously breathing rats, but accelerated heart rate in artificially ventilated animals. Blood pressure and heart rate of spontaneously breathing animals were not altered following nucleus ambiguus (NA) injection of DAGO or DADL (0.3 nmol), but were elevated in artificially respired animals; MRZ (3.0-10 nmol) injected into the NA depressed blood pressure in both groups. These data suggest that in the absence of respiratory depression, NTS and NA mu receptors mediate pressor responses and tachycardia; kappa receptors in the NA mediate a decrease in blood pressure but cardioacceleration in the NTS.

Animals↗