Typescript (photocopy). / Digitized by Kansas Correctional Industries

Vita. / Digitized by Kansas Correctional Industries

published_or_final_version / abstract / Zoology / Master / Master of Philosophy

Access to abstract permanently restricted to Ball State community only. / Access to dissertation permanently restricted to Ball State community only. / School of Physical Education, Sport, and Exercise Science

The mechanical and biochemical effects of prostaglandins E₁ and F₁α were studied on rat heart using isolated right and left atria and the Langendorff perfused whole heart preparation. Preliminary experiments were performed to establish optimal perfusion conditions for the Langendorff preparation. Hearts were perfused at different perfusate temperatures and at different filling pressures. Heart rate and coronary flow rate were monitored at all combinations of perfusate temperature and filling pressure. A constant temperature water recirculating pump setting of 38°C and a filling pressure of 40 cm of H₂O were chosen as the optimal perfusion conditions. Hearts perfused under the above conditions responded normally to bolus injections of isoproterenol. Isoproterenol produced a dose dependent increase in the contractile force of the Langendorff preparation and the cyclic AMP increasing effect of isoproterenol preceeded the positive inotropic effect in a time course study. Prostaglandin E₁ (PGE₁) did not produce any effect on heart rate or tension development in the Langendorff preparation, when infused over a dose range of 0.03 Ug to 5.0 μg/min. Infusion of prostaglandin F₁α (PGF₁α) (0.1 to 5.0 μg/min) produced an increase in tension development which was associated with a negative chronotropic effect. The positive inotropic effect of PGF₁α was secondary to the drop in rate as the positive inotropic effect was completely abolished when the hearts were paced at 6 Hz. In the rat right atrium, PGE₁ produced a dose dependent increase in the rate which developed very slowly. PGE₁ had no effect on the tension development of the.rat left atrium. PGF₁α produced a slow, dose dependent positive chronotropic effect on the right atrium and a slight but not significant effect on the force of contraction of the left atrium. Both prostaglandins were equipotent in exerting their positive chronotropic effect on the right atrium. The PD₁ value for PGE₁ was 5.54 ±0.25 and for PG₁α 5.59 ± 0.18. In the right atrium 10⁻⁴ M PGE₁ increased the rate and cyclic AMP content without changing phosphorylase a activity or cyclic GMP content. PGE₁ (10⁻⁴M) slightly but not significantly increased the left atrial cyclic AMP con-; tent and did not change the cyclic GMP content. 10⁻⁴ M PGF₁α did not affect either right or left atrial cyclic AMP or cyclic GMP content. The effect of a 1 μg/min infusion of either PGE₁ or PGF₁α on the changes of cyclic AMP and cyclic GMP contents and phosphorylase a activity with time were studied in the Langendorff preparation. A 1 μg/min infusion of PGE₁ increased the myocardial cyclic AMP levels by about 57 per cent above control at 30 sees after starting the infusion and the cyclic AMP levels were still elevated by 50 per cent over control at the end of a one minute period of infusion. PGE₁ did not change cyclic GMP content or phos-phorylase a activity at any time point. A 1 ug/min infusion of PGF₁α did not alter cyclic AMP and cyclic GMP levels or phosphorylase a activity in the rat heart within one minute. These results supported the earlier reported observation that PGE₁ selectively increased rat myocardial cyclic AMP content without altering myocardial contractile force or phosphorylase a activity. PGE₁ might be selectively increasing a pool of cyclic AMP and activating a cyclic AMP-dependent protein kinase in the cardiac cells that is not associated with contractile force or phosphorylase activation. PGF₁α did not possess this selective effect of PGE₁. Cyclic GMP is not involved in the mediation of the actions of either PGE₁, or PGF₁α, on the rat heart. / Pharmaceutical Sciences, Faculty of / Graduate

Prostaglandin E2 (PGE2), a byproduct of arachidonic acid metabolism, has been suspected to be involved in tumor promotion. It has been suggested that diet may modulate PGE2 level in organisms thus affecting the implantation and growth of the tumor tissue. PGE2 content was investigated in mice fed ad libitum four types of fatty acid diets: saturated fatty acid diets: a stearic acid and a palmitic acid, and polyunsaturated fatty acid diets: a low fat (safflower 1%) and a high fat diet (safflower 15%). Tumor cells were implanted subcutaneously in mice and harvested when tumors reached .05- 4g. The extracted PGE2 were derivatized and quantified by High Performance Liquid Chromatography (HPLC). The results showed that there is a negative correlation between the level of PGE2 and the size of the tumors. PGE2 level declined as the tumor grew. This suggests that during the early stage of growth the tumor requires higher level of PGE2 to boost its growth. As the tumor becomes more adapted to its environment, it no longer depends on PGE2 to survive. Diet was also seen to be important in tumor suppression. Saturated fatty acid diet (SA-1) showed a suppressive effect on tumor growth. A visual comparison showed that polyunsaturated high fat diet produced more PGE2 than saturated fatty acid. This high level of PGE2 correlate with the highest tumor weights obtained in the Polyunsaturated high fat diet group. / Department of Biology

The purpose of this study was to determine the effect of prostaglandin (PG) inhibition on the sympathetic and pressor responses to isometric handgrip (HG) at 40% of maximal voluntary contraction (MVC) to exhaustion and postcontraction muscle ischemia (PC). To accomplish this heart rate (HR), arterial pressure (n=10) and plasma norepinephrine (NE) levels (n=8) were measured in 10 healthy male subjects during HG at 40% of MVC to exhaustion and during PC. The subjects were given a double-blind administration of either placebo (PLAC) or a single 100 mg dose of indomethacin (IND). The order of administration was counterbalanced and a one week drug washout period was provided between conditions. Mean arterial pressure increased 25±5 vs. 22±4 mmHg during the second minute of HG and 26±2 vs. 21±5 during the last minute of PC in PLAC vs. IND (P>.05), respectively. Heart rate was increased 21±4 vs. 17±3 bpm during the second minute of HG in PLAC vs. IND (P>.05), respectively and returned to control values during PC in both trials. Plasma NE increased 343189 vs. 289±89 pg/ml after HG and 67514132 vs. 6324132 pg/ml after PC (P>.05) in PLAC vs. IND, respectively. Therefore, PG inhibition does not alter sympathetic or arterial pressure responses during sustained isometric exercise in humans. This may suggest that 1) PGs not important in metaboreceptor stimulation of sympathetic or pressor responses to sustained isometric contractions in humans or 2) PGs may play only a small role in the regulation of these variables which may be masked by the effects of other stimuli. Index terms: prostaglandins, pressor reflex, muscle sympathetic nerve activity, static exercise / Ph. D.

Abstract not available