Prostaglandins and pacemaker activity in isolated guinea pig SA node

Prostaglandins PGE2, PGE1, PGF2alpha, and PGE1 substantially increase automaticity in SA-nodal, right atrial preparations excised from guinea pigs. This natural pacemaker tissue is sensitive to nanomolar doses of PG with, for example, 10(-8) M PGE2, increasing SA rate by about 20%. If these preparations are pretreated with 2 micrometer indomethacin, a blocker of endogenous prostaglandin synthesis, then spontaneous rate drops and subsequent rate increases due to PGE2 administration can be more easily demonstrated. Guinea pig pacemaker tissue differs from similar rabbit tissue not only in that it is directly responsive to PGE2, but also in that PGE2 does not depress the absolute response to transmural stimulation (adrenergically mediated rate increase). The positive chronotropic responses to PGE2 also occur when the guinea pig tissue is pretreated in 0.6 micrometer propranolol, which causes blockade of beta-adrenergic receptors. The pacemaker myocardium in the guinea pigs thus appears to be directly stimulated by exogenous PGE2 at very low doses. The observation that 2 micrometer indomethacin reduces SA-nodal rate suggests the presence of a very sensitive, functionally important, PGE-like system which modulates heart rate in this mammalian species.