Changing the temperature, frequency of stimulation and calcium concentration altered the dose-response curves for isoproterenol and histamine on guinea pig and rabbit papillary muscles. Basal developed force, maximal developed force and sensitivity to the agonists were all affected. Increasing the temperature stepwise from 25° to 42° resulted in a progressive decrease in BDF and sensitivity to the agonists. The response of MDF was different in the guinea pig and rabbit. In the guinea pig, MDF was not affected by changing the temperature, and the size of the response to isoproterenol and histamine was similar. In the rabbit, the largest MDF response was seen at 37.5° when the calcium concentration was maintained at 2.2 mM. At this calcium concentration the response to histamine was less than that to isoproterenol at each temperature, although the difference was not significant. Increasing the frequency of stimulation stepwise from 0.5 to 4 Hz in the guinea pig, and 0.2.to 3 Hz in the rabbit affected the dose-response curves in a slightly different manner. In both species, BDF was reduced by low frequency stimulation. At other frequencies BDF was not changed. With isoproterenol, the MDF was only reduced by high frequency stimulation, and the sensitivity increased stepwise with increasing frequency. With histamine, the MDF was reduced by both low and high frequency stimulation. In the rabbit the response to histamine was consistently less than that to isoproterenol. The sensitivity to histamine was not affected by changing the frequency in the guinea pig, but was increased by high frequency stimulation in the rabbit. Increasing the calcium content stepwise from 1.5 to 8 mM in the guinea pig, and 0.5 to 6 mM in the rabbit resulted in a progessive increase in BDF, MDF and sensitivity. In both species, the increase in MDF appeared to reach a maximum between 2.2 and 6 mM calcium. In the rabbit this effect was less noticeable in situations where the frequency or temperature was also reduced. The response to histamine was reduced compared to that of isoproterenol. We postulate that the response to histamine is reduced in rabbit papillary muscles due to stimulation of H₁- receptors in this tissue. It has been shown that stimulation of β and H₂- receptors results in an increase in cyclic AMP, while stimulation of H₁- receptors has no effect on cyclic AMP. The increase in cyclic AMP may enhance calcium binding by the SR resulting in an augmented response.. In the guinea pig papillary muscle which contains β- and H^- receptors, the inotropic responses to isoproterenol and histamine are similar, while in the rabbit papillary muscle which contains 3- and H₁- receptors, the response to histamine is reduced compared to that of isoproterenol. This difference may be due to the lack of cyclic AMP involvement in the response to histamine in this tissue. Use of the calcium antagonist D600 produced a decrease in the sensitivity of rabbit papillary muscles to isoproterenol, but did not depress the MDF. There was no difference in the sensitivity to histamine. D600 therefore could not distinguish any difference in dependence on extracellular calcium between isoproterenol and histamine in this tissue. Isoproterenol stimulated an increase in ⁴⁵Ca content of rabbit right ventricle strips at 2 minutes after administration. No effect could be detected at any other time, nor when histamine was used. It is sugges- ted that at times greater than 2 minutes any increase in ⁴⁵Ca content induced by isoproterenol was masked by a "pool saturation" phenomenon, and that this increase which was detected is consistent with a difference in the mechanism of action of isoproterenol and histamine in rabbit ventricular muscle. / Pharmaceutical Sciences, Faculty of / Graduate

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 5 uppsatser.

Thesis (M.Sc.)--University of Adelaide, Dept. of Human Physiology and Pharmacology, 1973.

Thesis (M.S.)--Virginia Polytechnic Institute and State University, 1991. / 1 folded diagram. Vita. Abstract. Includes bibliographical references (leaves 85-87). Also available via the Internet.

Thesis--University of Wisconsin--Madison. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 514-525).

Thesis (M.S.)--University of Wisconsin--Madison, 1983. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 59-68).

The literature has provided ample evidence that neural influence is responsible for the regulation and maintenance of muscle properties. This study, conducted on approximately 100 mice of the C57 BL/6J+/+ species investigated the differential effects of denervation on the isometric contractile properties of a fast-twitch (extensor digitorum longus) and a slow-twitoh (soleus) muscle. Adult male animals were studied at 1, 28, 84 and 210 days following unilateral section of the sciatic nerve. The muscles were stimulated in vitro at 37°C at optimal length by supramaximal square pulses. The data for all muscles in each experimental group were pooled and compared to age-matched controls. In both the denervated soleus (SOL) and extensor digitorum longus (EDL) the time-to-peak twitch tension and the half relaxation were prolonged by 28 days post-denervation and this trend continued to the oldest age groups studied. The weight of the denervated muscles was less than that of the controls. Consequently, although the force that could be generated per unit mass by the EDL was initially well maintained, all muscles showed reduced peak tetanic tension in the long term, following denervation. Even when developed tension was expressed on a per wet weight basis, soleus became weaker with increased time post-denervation. A surprising and unexpected-result was the finding that 28 days after denervation both the fast and slow-twitch muscles developed increased tension. The denervated SOL showed a marked decrease in resistance to fatigue at 1 and 28 days, whereas the EDL showed an increase in resistance to fatigue at 28 days and beyond. It was concluded that denervation affected the tension generating ability and the contraction time of the SOL more than the EDL. The fatigue response indicated that conversion of fibre types may have occurred in the EDL and to a lesser extent in the SOL. The results support the hypothesis that slow muscle may be more dependant upon neural influence than fast muscle for the maintenance of its contractile properties. Further experiments to test this hypothesis are outlined. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

Thesis (Ph. D.)--Florida State University, 2005. / Advisor: Peter G. Fajer, Florida State University, College of Arts and Sciences, Dept. of Biological Science. Title and description from dissertation home page (viewed Jan. 26, 2006). Document formatted into pages; contains xiii, 161 pages. Includes bibliographical references.

Mammalian myocardial contractility is believed to be regulated by the amount of calcium contained in a highly labile superficial calcium pool. The purpose of the first part of this study was to determine the role of such sites in the positive inotropic effect of isoproterenol. Lanthanum, an ion known to be restricted to the extracellular space and which displaces the superficially-bound calcium, was selected as a tool for this investigation. In Langendorff preparations of the guinea pig heart, lanthanum decreased the basal contractility index (+dP/dtmax) in a concentration-dependent fashion (0.05-3 µM) and blocked the inotropic response of isoproterenol in a non-competitive manner (0.25-3 µM). Three µM lanthanum: 1) reduced basal contractility and the maximum response to isoproterenol by 97 and 95%, respectively; 2) had no significant effect (p>0.05) on basal and isoproterenol-induced cyclic AMP levels; and 3) had no effect on the kd of [³H]nitrendipine binding, but reduced the Bmax by 31%. While 1 µM lanthanum reduced basal contractility and the maximum response to isoproterenol by 90 and 70%, respectively, it had no effect on [³H]nitrendipine binding. These results suggest that the effects of such low concentrations of lanthanum (≤3 µM) are not related to a direct action on the calcium channels and are not mediated by an inhibition of isoproterenol stimulation suggest that superficially-bound calcium is required for the inotropic response of isoproterenol. The purpose of the second part of this study was to elucidate the biochemical nature of the superficial calcium binding sites, the sialic acids in particular, in the inotropic response of cardiotonic agents. To determine the role of the glycocalyx residues of sialic acids in excitation-contraction coupling and the inotropic response to cardiotonic agents, I studied the effect of removal of the sialic acids following neuraminidase treatment on the response to ouabain, isoproterenol, calcium and reduced extracellular sodium in Langendorff preparations of adult guinea pig hearts. Neuraminidase treatment (0.01 U/ml, 1 h) reduced the magnitude of the positive inotropic response to 2.5x10⁻⁷M ouabain and the maximum response to 5x10⁻⁷ M ouabain by about 46 and 30%, respectively, but did not prevent ouabain toxicity. Neuraminidase treatment did not affect the contractility produced by calcium concentration alterations up to 5 mM calcium or the positive inotropic effect produced by lowering external sodium to as low as 80 mM. The inotropic response to as high as 10⁻⁸ M isoproterenol was also not affected. The contractility response developed to calcium concentrations greater than 5 mM and to 5x10⁻⁸ M isoproterenol were significantly reduced (p<0.05) by neuraminidase treatment. The content of sialic acids in neuraminidase-treated hearts used in the above concentration-response reduced by 70.7, 66.1, 65.6 and 66.2%, respectively. Neuraminidase treatment had no effect on basal (Na⁺-K⁺)ATPase and Mg²⁺ -ATPase activities of (Na⁺-K⁺)ATPase-containing membrane preparations of the guinea pig left ventricle. Neuraminidase treatment neither influenced the sensitivity of the enzyme (Na⁺-K⁺)ATPase to ouabain inhibition nor did it affect the characteristics of [³H]ouabain binding to the preparation. These results suggest that the sialic acids of the glycocalyx in the guinea pig left ventricle play an important role in part of the inotropic response to subtoxic concentrations of ouabain. / Pharmaceutical Sciences, Faculty of / Graduate

Thesis (doctoral)--Lund University, 1994. / Added t.p. with thesis statement inserted.