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
| Identifer | oai:union.ndltd.org:UBC/oai:circle.library.ubc.ca:2429/22188 |
| Date | January 1979 |
| Creators | Vadlamudi, Rao Venkata Satya Veerabhadra |
| Source Sets | University of British Columbia |
| Language | English |
| Detected Language | English |
| Type | Text, Thesis/Dissertation |
| Rights | For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use. |
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