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Biomedical subjects

T E Tenner

Publications and source records attributed to T E Tenner.

At least 55 records · Page 3Linked to original sources
PubMed1981

The characterization of cardiac histaminergic chronotropic receptors in the rabbit.

The effects of selective histamine receptor analogs were studied in spontaneously beating rabbit atria. Atrial rate was increased by histamine (an H1 and H2 agonist), 4-methylhistamine and impromidine (H2 agonists), and 2-pyridylethylamine (PEA, an H1 agonist). The responses to histamine, 4-methylhistamine, and impromidine were not affected by propranolol (1 x 10(-7) M) or reserpine pretreatment. However, the response to PEA was nearly abolished upon pretreatment with propranolol or reserpine. Cimetidine pretreatment (H2 receptor blockade) competitively antagonised the positive chronotropic effects of histamine, 4-methylhistamine, and impromidine. Promethazine pretreatment (H1 receptor blockade) competitively blocked the chronotropic effects of histamine but had no effect on the responses to 4-methylhistamine or impromidine. These results suggest that stimulation of H1 and H2 receptors will cause a positive chronotropic response.

Animals↗
PubMed1981

Comparison of H2 receptor agonists in rabbit atria and aorta.

In an effort to compare the H2 receptors responsible for the chronotropic and vasorelaxant effects of histamine, rabbit right atria and aortae were studied using four H2 receptor agonists and the H2 receptor antagonist cimetidine. While the efficacies of the various agonists were not similar in the two tissues, the order of potency in both atria and aortae was impromidine greater than histamine greater than 4-methylhistamine greater than dimaprit. In addition, cimetidine, an H2 receptor antagonist, inhibited the chronotropic and relaxant effects of impromidine and histamine in a consistent fashion in both atria and aorta. The results obtained in the present study are consistent with the concept that the H2 receptors in rabbit atria and aortae represent one type of receptor and not two isoreceptors as is the case for beta-adrenergic receptors in these tissues.

Animals↗
PubMed1981

Lack of histamine involvement in parathyroid hormone hypotensive action.

Promethazine and cimetidine blocked the hypotensive actions of 2-pyridylethylamine, and H1 agonist and dimaprit, an H2 agonist, respectively, but not that of bovine parathyroid hormone fragment [bPTH-(1-34)]. Rats were treated repeatedly with the histamine releaser, compound 48/80, until the release could no longer produce a decrease in blood pressure. The hypotensive action of bPTH-(1-34) could still be seen. Rats with histamine partially depleted with one injection of compound 48/80 were injected with cimetidine and pyrilamine, and H1 antagonist, which together blocked the hypotensive action of subsequent injections of compound 48/80, but not that of bPTH-(1-34). These data suggest that the vasodilatory action of bPTH-(1-34) does not involve the release or action of histamine.

Animals↗
PubMed1981

Hypotensive action of synthetic fragments of parathyroid hormone.

Parathyroid hormone (PTH) and its N-terminal 1-34 fragment were shown to be hypotensive in dogs. In this study, synthetic bovine PTH fragments containing the N-terminal amino acids 1-34, 24-34, 24-28 and 25-27 [bPTH-(1-34), bPTH-(24-34), bPTH-(24-28) and bPTH-(24-27)] were synthesized and tested for hypotensive activity in dogs. bPTH-(1-34) is the most potent of these. The tripeptide is ineffective at doses as high as 2 mg/kg. bPTH-(24-34) and bPTH-(24-28) exhibited hypotensive activity but were less effective than bPTH-(1-34). A decrease in chain length decreased the hypotensive activity. The maximum response produced by bPTH-(1-34) was greater than that of either bPTH-(24-34) or bPTH-(24-28). The maximum responses, however, of bPTH-(24-34) and bPTH-(24-28) were similar. Another striking difference between bPTH-(1-34) and the other two effective fragments was the duration of action. Whereas the action of bPTH-(1-34) at ED50 lasted for up to 6 min the action of bPTH-(24-34) and bPTH-(24-28) lasted for less than 1 min. The hypotensive effect of these three bPTH fragments was not affected by propranolol, phentolamine, atropine, promethazine or cimetidine. In the perfused rat hindlimb, bPTH-(24-28) produced log dose-related sustained vasodilation.

Animals↗
PubMed1980

Pharmacological comparison of bPTH-(1-34) and other hypotensive peptides in the dog.

The purpose of the present study was to compare the potency, effectiveness and duration of action of synthetic bPTH-(1-34) with those of other known hypotensive peptides in the anesthetized dog. Of sixteen peptides tested in the present study only 8 were demonstrated to possess hypotensive activity. While bPTh-(1-34) was one of the least potent of the hypotensive peptides, it was equal to or greater than the other peptides in terms of effectiveness and duration of action. Of all the peptides studied, substance P and eledosin were the most potent in terms of their hypotensive action. It is suggested that perhaps substance P and eledoisin might act at a different site or through different mechanisms than do vasoactive intestinal peptide (V.I.P.), corticotropin inhibiting peptide (C.I.P.), neurotensin, xenopsin, bradykinin and bPTH-(1-34).

Adrenocorticotropic Hormone↗
PubMed1980

Hypotensive action of parathyroid hormone preparations on rats and dogs.

Bovine parathyroid extract and two commercial preparations containing the first 34 amino acids of synthetic bovine parathyroid hormone [bPTH-(1-34)]produced dose-related hypotension in anesthetized rats. Dogs were 10 times more sensitive to the two bPTH-(1-34) preparations than were rats. Propranolol, phentolamine, atropine, and promethazine did not affect the hypotensive action of bPTH-(1-34) in rats and dogs. bPTH-(1-34) decreased perfusion pressure in rat hindlimbs perfused in situ with Ringer's solution and was a vasodilator in dog kidneys perfused in vitro with Ringer's solution. Helical strips of rabbit aorta were also relaxed by bPTH-(1-34). We conclude that the direct vasodilatory action of bPTH preparations represents an intrinsic property of parathyroid hormone and that the hypotensive effect of this hormone is produced by part or all of the first NH2-terminal 34 amino acids.

Adrenergic alpha-Antagonists↗
PubMed1980

Interaction of clonidine with chronotropic agents on isolated right atria.

Clonidine was administered to isolated guinea pig right atria in order to characterize its chronotropic activity and its interaction with other chronotropic agents at the postjunctional level. Clonidine either had no significant effect (10(-7)--10(-4) M) or decreased (10(-3) M) atrial rate. Pretreatment of the atria with clonidine noncompetitively antagonized (10(-6)--10(-4) M) the positive chronotropic actions of isoproterenol, and competitively antagonized (10(-4) M) the negative chronotropic actions of pilocarpine. At doses of 10(-6) or 3 X 10(-6) M, clonidine also noncompetitively antagonized the positive chronotropic effects of 4-methylhistamine and glucagon. The results show that clonidine antagonizes both adrenergic and cholinergic influences on atrial rate at the postjunctional level and suggest that the antagonism of adrenergic influences does not involve a direct interaction with beta-adrenergic receptors.

Animals↗
PubMed1980

Cardiac histamine receptors.

Histamine can produce inotropic and chronotropic responses in both guinea pig and rabbit heart. In the guinea pig the responses are mediated primarily through stimulation of H2 receptors with H1 receptors being found mainly in left atria. In the rabbit H1 receptors predominate; H2 receptors are found only in right atria and are partially responsible for the chronotropic effect. H2 receptors are always associated with cyclic AMP, whereas H1 receptors are not. H2-histamine receptors and beta-adrenergic receptors have a number of properties in common. Stimulation of either receptor results in positive inotropic and chronotropic effects and increases in cyclic AMP and phosphorylase a. H2 and beta-adrenergic agonists will also both restore the action potential in K+-depolarized cardiac muscle. H1 and alpha-agonists, on the other hand, will also produce an inotropic effect. The effect is not dependent on cyclic AMP and can only be demonstrated under certain conditions. Neither agonist will restore the action potential in depolarized cardiac tissue. It is concluded that, although H2 and beta-agonists and H1 and alpha-agonists may have a common mechanism of action, the two groups of drugs (H2, beta versus H1, alpha) differ from each other with regard to mechanism.

Animals↗
PubMed1978

Effect of extracellular Na on isoproterenol-induced cAMP levels in depolarized uterus.

In the present study, the absence of a quantitative correlation between isoproterenol induced relaxation of uterine strips and tissue cAMP levels was demonstrated by using three depolarizing media: 127 mM KCl (0 NaCl), 47.5 mM KCl (NaCl), and 47.5 mM KCl (80 mM NaCl). While the degree of relaxation by isoproterenol was similar in all three media, isoproterenol (10(-4)M) increased cAMP by 100% in Na+ free depolarizing media, by 337% in Na+ containing depolarizing medium and by 600% in normal non-depolarizing medium. After pretreatment of the tissue with 10(-5) M D-600, 10(-4) M isoproterenol increased cAMP levels by 600% in all three depolarzing media. Studies using 10(-8) M isoproterenol produced qualitatively similar results. cGMP levels did not change significantly in any of the above studies. Na+ appears to be producing its effect on isoproterenol induced increase in cAMP levels indirectly by reducing the increase in intracellular Ca2+ concentration known to occur with depolarization.

Animals↗
PubMed1978

Reserpine-induced supersensitivity to the inotropic and phosphorylase activating effects of glucagon in the perfused rat heart.

Glucagon (0.125--2.0 microgram) produced a dose-dependent increase in cyclic AMP, % phosphorylase a and force of contraction in the isolated perfused rat heart. Pretreatment of animals with reserpine (2.5 mg/kg, 24 h) resulted in an enhancement of the inotropic and phosphorylase activating effects of glucagon but the effect on cyclic AMP was not altered. It is suggested that reserpine-induced supersensitivity in the rat heart occurs at a point beyond the cyclic AMP step.

Animals↗
PubMed1978

The role of calcium in supersensitivity to the inotropic effects of norepinephrine.

Experiments using electrically stimulated rabbit left atria have demonstrated that supersensitivity to the inotropic effects of norepinephrine can be induced by either chronic reserpine pretreatment or hypothermia (lowering the temperature of the bathing medium). These two experimental conditions for inducing supersensitivity were not additive implying that they shared a common mechanism of action. Norepinephrine had no significant effect on the amplitude of a potentiated contraction of the rabbit atrium when the temperature was reduced from 37 to 30 degrees C or following pretreatment with reserpine (30 or 37 degrees C). Under these same conditions the ED50 of norepinephrine on the normal contraction was reduced. It is concluded that both reserpine pretreatment and hypothermia induce supersensitivity to the inotropic effects of norepinephrine by enhancing the cellular store of activator calcium while not affecting the ability of norepinephrine to release activator calcium.

Animals↗
PubMed1978

Characterization of the inotropic response induced by stimulation of beta-adrenergic and H1 histaminergic receptors in guinea pig left atria.

The inotropic response induced by beta-adrenergic and H1 histaminergic receptor stimulation was characterized in guinea pig left atria by obtaining dose-response relationships for isoproterenol and histamine under various experimental conditions. Conditions (hypothermia, high frequencies of stimulation, and large extracellular calcium concentrations) which enhanced the ability of cardiac muscle to develop force also increased the sensitivity of the left atrium to isoproterenol while decreasing its efficacy. On the other hand, conditions which enhanced the ability of cardiac muscle to develop force depressed the efficacy of histamine to such an extent that the sensitivity to histamine was also decreased. In addition, conditions which markedly depressed the ability of cardiac muscle to develop force also decreased the efficacy and sensitivity to histamine. The data indicate that while beta-adrenoceptor stimulation results in an inotropic response under all conditions studied, stimulation of H1 histaminergic receptors results in an inotropic response only within a narrow range of experimental conditions.

Animals↗