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Biomedical subjects

T E Tenner

Publications and source records attributed to T E Tenner.

At least 37 records · Page 2Linked to original sources
PubMed1987

Alterations in the myocardial beta-adrenoceptor system of streptozotocin-diabetic rats.

Previous investigations in our laboratory revealed subsensitivity of right ventricular tissue, isolated from one month STZ-diabetic rats, to the inotropic effects of isoproterenol. The present study was concerned with the characterization of this subsensitivity phenomenon. Observations of supersensitivity to methoxamine accompanied by decreased responsiveness to glucagon without a change in responsiveness to forskolin suggested a specific effect of diabetes on pathways involving receptor-mediated activation of adenylate cyclase. Radioligand binding analysis further revealed a specific decrease in the population of the high affinity state of the beta-adrenoceptor. Since the high affinity receptor state is a necessary intermediate for adenylate cyclase activation and enhanced myocardial contractility, it is proposed that the specific decrease in the high affinity population of the beta-adrenoceptor contributes to myocardial subsensitivity to isoproterenol observed in the diabetic animals. It is further proposed that the decrease in receptor population is related to increases in circulating epinephrine levels which were evident in the diabetic animals.

Animals↗
PubMed1987

Prevention of streptozotocin-induced alterations in the rat heart by 3-O-methyl glucose and insulin treatments.

Streptozotocin-induced diabetes has previously been shown to alter the sensitivity and responsiveness of rat myocardial tissues to cardiotonic agonists. The objective of the present study was to determine if these alterations were due to the diabetogenic or possible direct cardiotoxic effects of streptozotocin. One month after streptozotocin treatment the following changes were observed in the rat: decrease in body weight; elevation of blood glucose and glycosylated hemoglobin levels; decrease in spontaneously beating atrial rate; elevation in basal developed force of electrically driven right ventricle; and inotropic subsensitivity of right ventricle to isoproterenol, which was associated with decreased beta-adrenoceptor density and supersensitivity to calcium. Pretreatment with the nonmetabolizable glucose analog 3-O-methyl glucose prevented these alterations. Chronic insulin replenishment also reversed the effects of streptozotocin, with the exception of complete normalization of elevations in blood glucose and basal developed force. Acute exposure to high glucose in the medium preserved the subsensitivity to isoproterenol but resulted in an elevated basal developed force in both control and streptozotocin groups. These observations indicate that myocardial alterations after streptozotocin treatment are not the result of direct cardiotoxic effects but rather a consequence of the drug-induced diabetic state. They also suggest that the increase in basal developed force might be related to elevated glucose concentrations.

3-O-Methylglucose↗
PubMed1986

Chronic effects of streptozotocin diabetes on myocardial sensitivity in the rat.

One month after streptozotocin treatment, basal rate in spontaneously beating right atria was decreased and basal developed force in electrically-driven right ventricular tissue was increased. Atrial sensitivity to the chronotropic effects of isoproterenol was not altered. In contrast, sensitivity in ventricular tissue to the inotropic effects of isoproterenol was decreased while sensitivity to calcium was increased. Associated with these changes was a decrease in myocardial beta-adrenoceptor density. Data obtained 3 and 6 months after streptozotocin treatment were similar to the observed alterations at 1 month. These results suggest that alterations in the chronotropic and inotropic responses that are expressed within 1 month after streptozotocin treatment do not significantly progress during the 6 months following induction of diabetes. They therefore reveal the independence of myocardial alterations from age of the animal and duration of diabetes (up to 6 months).

Animals↗
PubMed1986

Cyclic AMP and the vascular action of parathyroid hormone.

The involvement of tissue cAMP in the vasodilating action of parathyroid hormone (PTH) was investigated. The bovine active fragment bPTH-(1-34) was used in all studies. In anesthetized dogs, theophylline, a phosphodiesterase inhibitor, potentiated the hypotensive action of bPTH-(1-34) at the dose of 1 microgram/kg. The potentiation was related to the dose of theophylline infused. In an in vitro rat tail artery helical strip assay, dibutyryl cAMP produced dose-related relaxation in arginine vasopressin (AVP) constricted blood vessels. bPTH-(1-34) also produced dose-related relaxation in the tail artery constricted by AVP. In the presence of isobutylmethylxanthine, another phosphodiesterase inhibitor, the bPTH-(1-34) dose--response curve was shifted to the left, indicating potentiation. Imidazole, which has phosphodiesterase stimulating activity, significantly decreased the in vitro vasorelaxing effect of bPTH-(1-34). In addition, bPTH-(1-34) increased significantly the rat tail artery cAMP content. b-PTH-(1-34) oxidized with hydrogen peroxide lost its vasorelaxing activity and was also ineffective in increasing the tail artery cAMP content. All these data strongly suggest that cAMP may be involved in eliciting the vasorelaxing action of bPTH-(1-34).

1-Methyl-3-isobutylxanthine↗
PubMed1985

The vasorelaxant action of parathyroid hormone fragments on isolated rat tail artery.

Previous studies have demonstrated that parathyroid hormone (PTH) and its 1-34 amino terminal fragment possess a hypotensive action in vivo which appeared to be direct and dose-dependent. However, attempts to demonstrate the phenomenon in isolated vascular tissue have been minimally successful at best. The present study reports that bovine PTH-(1-34) can relax isolated rat tail artery helical strips precontracted by either arginine vasopressin, depolarizing concentrations of potassium chloride, or norepinephrine. The phenomenon occurs in a dose-dependent manner and is not dependent upon the presence of the endothelial lining of the vessels. These studies support the hypothesis that bovine PTH-(1-34) produces a direct vasorelaxant action mainly in small arteries.

Animals↗
PubMed1984

Alterations in aortic and tail artery reactivity to agonists after streptozotocin treatment.

In the present study, responses to various agonists in thoracic aorta and tail artery strips, obtained from 4-week streptozotocin (STZ)-treated rats and age-matched controls, were studied. Responses in aorta obtained from diabetic animals to the alpha-agonists, norepinephrine (NE), and methoxamine (MOX), to calcium (Ca2+) and potassium (K+) were found to be depressed relative to control tissue. Responses in tail artery however, were found to be different. While responses to K+ were decreased and to Ca2+ unchanged, tail artery strips obtained from diabetic animals were found to be supersensitive to both alpha-agonists relative to control tissue. Another observed difference between the two tissues was in their catecholamine content. While induction of diabetes did not alter catecholamine levels in the aorta, a significant decrease was produced in the tail artery, relative to control tissue levels. Our results indicate that inherent differences (such as the degree of innervation) may contribute to the differential responses observed in the two tissues studied. They further suggest the possible involvement of alterations in calcium utilization in aorta and the development of postjunctional supersensitivity in tail artery obtained from STZ-treated animals.

Animals↗
PubMed1983

Propranolol withdrawal-induced supersensitivity to the chronotropic effects of isoproterenol in the conscious rabbit.

The present study was undertaken to determine if chronic administration and abrupt withdrawal of propranolol would induce supersensitivity to the chronotropic effects of isoproterenol in the conscious rabbit. Eight rabbits were pretreated with propranolol (40 mg/kg/day, i.p.) for one week. Dose-response curves were obtained one week prior to pretreatment and 24, 48, 72 and 168 hours after the last dose of propranolol. Isoproterenol (0.01 to 10 micrograms/kg) was injected via the marginal ear vein and heart rate was monitored continuously by recording the ECG. During the withdrawal period no significant rebound increase in basal heart rate was noted. Geometric mean ED50 values and their corresponding 95% confidence intervals were calculated and used as an index of potency. Twenty-four hours after withdrawal of propranolol pretreatment, the ED50 value for isoproterenol was significantly greater than control indicating continued surmountable beta-adrenoceptor blockade. In contrast, 72 hours after withdrawal, the geometric mean ED50 value was significantly less than control. The maximum chronotropic response to isoproterenol was not found to be different from control at any time during the withdrawal period indicating that a change in responsiveness was not induced. These data are interpreted as evidence of a true supersensitivity to the chronotropic effects of isoproterenol in the conscious rabbit following propranolol withdrawal.

Animals↗
PubMed1983

Propranolol withdrawal supersensitivity in rat cardiovascular tissue, in vitro.

The purpose of the present study was to determine if propranolol withdrawal supersensitivity could be demonstrated under in vitro conditions. Rats pretreated for 14 days with propranolol were studied 24, 48, 72 and 96 h after propranolol withdrawal. Right atria, right ventricle strips and thoracic aortic strips were isolated for study under in vitro conditions. Dose-response curves and geometric mean ED50 values revealed the presence of supersensitivity to the chronotropic and inotropic effects of isoproterenol in vitro at 72 and 96 h after withdrawal. No change in sensitivity was found 24 or 48 h after propranolol cessation. In like manner, supersensitivity to the vasorelaxant action of isoproterenol was demonstrated in aortic strips precontracted with angiotensin II at 72 and 96 h after propranolol withdrawal. In contrast, subsensitivity to the contractile actions of methoxamine was observed 48 h after withdrawal. These data indicate that chronic propranolol pretreatment and withdrawal results in the unmasking of supersensitivity to both beta 1 and beta 2 adrenoceptor stimulation. There would also appear to be a compensatory change in alpha-adrenoceptor-induced responses in rat aorta following propranolol withdrawal.

Animals↗
PubMed1983

Effect of insulin replacement on streptozotocin-induced effects in the rat heart.

Streptozotocin (65 mg/kg) was used to induce diabetes in male Sprague-Dawley rats. Isolated cardiac tissue exhibited a systematic depression in atrial pacemaker function and an enhancement in ventricular function accompanied by a supersensitivity to calcium relative to control animals. beta-Adrenoceptor density was found to be significantly lowered in the treated animals. However, no change in responsiveness of the tissues to isoproterenol was observed. The systematic changes in atria and ventricle were found to be completely and partially reversed respectively, by daily administration of 4-5 units of Ultralente (U-100) insulin, whereas the decrease in beta-adrenoceptor number and supersensitivity to calcium were completely reversed. These results suggest that STZ by itself might not have toxic effects in the heart and that its effects may be overcome by chronic insulin-replacement.

Animals↗
PubMed1983

Chronotropic actions of bPTH-(1-34) in the right atrium of the rat.

Bovine parathyroid hormone and its N-terminal (1-34) peptide fragment (bPTH-(1-34] are known to possess direct hypotensive activity in the rat. The purpose of the present study was to determine if bPTH-(1-34) possessed a direct chronotropic action as well. In vivo studies revealed that bPTH-(1-34) did produce a chronotropic effect in the rat comprising both a direct component as well as a reflex tachycardia related to its hypotensive actions. In vitro studies of isolated right atria indicated that while bPTH-(1-34) had no positive inotropic effect, it did produce significant chronotropic effects which were direct and dose-dependent. The potency of bPTH-(1-34) was found to be similar to that of isoproterenol, however, it was only one-third as effective as isoproterenol in maximally increasing atrial rate. A slight but significant increase in atrial cyclic AMP was generated prior to the chronotropic actions of bPTH-(1-34).

Adrenergic Fibers↗
PubMed1983

Alterations in cardiac performance in experimentally-induced diabetes.

Responses in cardiac tissue isolated from streptozotocin (STZ)-treated and age-matched control rats to isoproterenol (ISO) and calcium were studied. 4 weeks after STZ, atrial function was found to be depressed, whereas right ventricular function was enhanced. Neither tissue exhibited an alteration in sensitivity to ISO. In contrast, while sensitivity to calcium was found to be unaltered in atrial tissue, supersensitivity to calcium was observed in ventricles after STZ treatment. beta-Adrenoceptor number determination revealed a 36% decrease in Bmax with no change in affinity after STZ treatment. These results suggest that 4 weeks after STZ treatment pacemaker function is depressed, while enhancement in ventricular function is associated with an alteration in calcium utilization.

Animals↗
PubMed1982

Reserpine-induced supersensitivity and the proliferation of cardiac beta-adrenoceptors.

Chronic reserpine pretreatment resulted in an increase in the basal developed force generated by papillary muscles isolated from the right ventricle of the rabbit. In addition, supersensitivity to the inotropic effects of isoproterenol and a concomitant increase in beta-adrenoceptor number were demonstrated. These results indicate that reserpine-induced supersensitivity is not only associated with alterations at sites beyond the level of receptor activation but also at the level of specific postjuctional membrane receptors.

Adrenergic beta-Agonists↗
PubMed1982

Structure and vascular activity relationship of parathyroid hormone and some hypotensive peptides.

The synthetic fragment of bovine PTH [bPTH-(1-34)] had direct vasodilatory action in the coronary, renal, hepatic and some visceral vascular beds. The vascular action of bPTH-(1-34) was separable from its hypercalcemic action. We attempted to identify the amino acid sequence responsible for this vascular action. The methionines in positions 8 and 18 were not necessary for vascular relaxation since [Nle8, Nle18, Tyr34]-bPTH-(1-34) was active. However, when these methionine residues were oxidized, the vascular action of this peptide disappeared. This would suggest conformational changes of this oxidized peptide, resulting in loss of activity. Adjacent basic amino acids in positions 25, 26 and 27 may play an important role in the hypotensive action of peptides. Other hypotensive peptides such as neurotensin, xenopsin and VIP which also possess adjacent basic amino acids but are not known to be vasoactive were also hypotensive in our assays.

Animals↗