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J A Schriefer

Publications and source records attributed to J A Schriefer.

13 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↗
PubMed1993

Modulatory effect of endopeptidase inhibitors on bradykinin-induced contraction of rat uterus.

Bradykinin (BK) affects a variety of smooth muscle types, including uterus. These effects are generally short-lived due to metabolism by a variety of enzymes including angiotensin converting enzyme (ACE), endopeptidase 24.11 (EP-24.11) and endopeptidase 24.15 (EP-24.15). The uterotonic action of BK and the limitation of that action by peptidases were examined using isolated rat uterus. BK contracted the estrus, diestrus and day 22 pregnant rat uterus. N-[1(R,S)-carboxy-3-phenylpropyl]-Phe-p-aminobenzoate (10(-7) M), a specific inhibitor of EP-24.11, and N-[1(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (10(-6) M), a specific inhibitor of EP-24.15, enhanced BK-induced contraction in the estrus and pregnant uterus. Enalaprilat (6 x 10(-8) M), an inhibitor of ACE, also enhanced BK-induced contraction. The enzyme inhibitors alone did not contract the uterus. Bradykinin B2 receptor antagonism blocked the effects of the inhibitors. ACE is present in the rat uterus, but there are no reports of EP-24.11 or EP-24.15. Here we report that EP-24.11 and EP-24.15 activities are present in the estrus and pregnant rat uterus. Partially purified uterine homogenates metabolized specific model substrates for EP-24.11 and EP-24.15. The enzyme activities were inhibited by N-[1(R,S)-carboxy-3-phenylpropyl]-Phe-p-aminobenzoate and N-[1(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate, respectively, and increased 5- to 8-fold at term pregnancy as compared to estrus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Diethylstilbesterol- and pregnancy-induced changes in rat neurointermediate lobe oxytocin, arginine vasopressin, methionine enkephalin and dynorphin.

The neurointermediate lobe of the pituitary (NIL) contains the opioid peptides methionine enkephalin (MENK) and dynorphin 1-8 (DYN) in addition to oxytocin (OT) and vasopressin (AVP). If the opioids have a functional role, such as feedback control on OT or AVP release, the content or release of the opioids might be expected to change under conditions in which OT or AVP change. This expectation was examined by studying the synthesis, storage and release of the 4 peptides under conditions in which OT and AVP dynamics are known to be altered. Diestrus, diethylstilbesterol(DES)-treated, and day 22 pregnant rats were decapitated, the hypothalamo-neurohypophysial system (HNS) excised and either superfused in oxygenated Krebs buffer at 37 degrees C or stored at -80 degrees C for measurement of paraventricular and supraoptic nuclei mRNA content by in situ hybridization analysis. Peptide content of superfusates and NIL homogenates were determined by specific RIAs. Compared with diestrus animals, DES treatment increased NIL OT but decreased MENK. In term pregnant rats, NIL OT, AVP, and DYN were increased over diestrus values, while MENK was again decreased. Release of the peptides from the isolated HNS paralleled changes in NIL content. The hypothalamic mRNA for OT was increased in DES-treated and pregnant rats while MENK mRNA was decreased. AVP and DYN mRNA was increased in pregnant animals. Although the NIL was found to contain much more immunoreactive OT and AVP than MENK or DYN, under basal conditions the release of MENK was equal to or greater than the release of OT, while the release of DYN approached that of AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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↗
PubMed1982

Role of fetal oxytocin in parturition in the rat.

The oxytocin (OT) content of pituitary glands from neonatal rats was reduced by parturition, indicating possible release from fetal glands during labor. The content of fetal glands fell from 2.5 ng/gland in utero to 1 ng/gland immediately after birth. Rabbit serum antibodies against OT were administered to pregnant or fetal rats preceding parturition or to lactating rats on Day 10 of lactation. Antibody administration to lactating rats resulted in a decrease in weight gain of suckling pups, indicating that OT was bound by antibody. Administration of OT antibody to pregnant rats had no effect on the duration of gestation while injection into fetal pups resulted in an 18 h increase in the mean duration of gestation compared to sham-injected controls. These studies indicate that fetal OT might have a role in initiating parturition in the rat.

Animals↗
PubMed1980

Examination of dihydrotachysterol-induced progeria as a model for aging changes in carbohydrate metabolism.

Interest in the pharmacological effects of drugs in the elderly has created a need for a laboratory model in which responses of aged animals to drugs can be studied. Dihydrotachysterol (DHT)-induced progeria, a syndrome with symptoms similar to those seen in normal aging, was evaluated as an old age model. DHT-treatment was shown to produce a decreased carbohydrate tolerance that was due to an impaired release of insulin from pancreatic islets and not due to a decreased sensitivity to insulin. These changes were unlike those observed with aging. Thus, DHT-induced progeria would not appear to be a good model for aging for the investigation of carbohydrate metabolism. Evidence is presented which indicates that glucose and tolbutamide act via different mechanism to stimulate insulin release.

Aging↗
PubMed1980

Effect of dopamine on length of gestation and on the release of fetal oxytocin in rats.

Oxytocin (OT) release from the maternal posterior pituitary gland has been implicated in the process of spontaneous labor. The possibility that OT release from a fetal source may also be involved in this process was investigated. Administration of dopamine (DA), 150 mg/kg/ui hr, or L-dopa, 200 mg/kg/12 hr, plus carbidopa, 20 mg/kg/12 hr, to pregnant rats beginning on day 16 of gestation delayed the mean delivery time by 10 to 18 hr. These drug treatments also inhibited the release of OT from fetal pituitary glands which normally occurred during parturition. Release of OT from maternal pituitary glands was not affected and no alterations in the duration or outcome of labor were noted. Administration of [3H]DA to pregnant rats resulted in higher amounts of labeled DA in fetal brain tissues than in maternal brain. These studies suggest that fetal OT is involved in the timing of parturition in the rat and that DA may prolong gestation by affecting fetal OT.

Animals↗
PubMedDate not supplied

Care management.

Explore the source record for details and available documents.

Case Management↗
PubMedDate not supplied

Health outcomes skills for care management.

There are several skills nurses can develop or expand to improve their ability to manage outcomes. This is an exciting area for nurses and one that is valued during times of cost reduction in healthcare. In addition to increasing skills in the health outcomes management arena, nurses will benefit from a continual increase in knowledge of case management, clinical pathways, and guidelines. The healthcare market-place is likely to reward nurses with these skills.

Case Management↗