The cardiovascular and platelet effects of epoprostenol (prostacyclin, PGI2) are unaffected by beta‐adrenoceptor blockade in man.

Abstract

1 Atenolol 0.2 mg/kg i.v., propranolol 0.2 mg/kg i.v. or placebo were given in a double‐blind crossover study to six healthy male subjects, and the effects of a subsequent infusion of epoprostenol (prostacyclin, PGI2) 0‐6 ng kg‐1 min‐1 monitored. 2 PGI2 caused a tachycardia, a fall in diastolic blood pressure, a rise in pulse pressure, reduction in pre‐ ejection period (PEP) and rise in left ventricular ejection time index (LVETI), headache and facial flushing at doses of PGI2 greater than 2 ng kg‐1 min‐1, (P less than 0.05). 3 Beta‐adrenoceptor blockade did not prevent the tachycardia in response to PGI2, and did not interact with any of the other dynamic effects of PGI2. 4 In vitro, PGI2 at 1 and 2 ng/ml inhibited platelet aggregation to ADP (P less than 0.01), although no significant effect on platelet aggregation was seen in the in vivo study. Atenolol and propranolol at a final concentration of 1 microgram/ml did not affect this in vitro study. Atenolol and propranolol at a final concentration of 1 microgram/ml did not affect in vitro effect of PGI2 on platelet aggregation. 5 Pretreatment with atropine 0.04 mg/kg i.v. in three subjects did not attenuate the tachycardia caused by PGI2 infusion, even though the baseline heart rate was increased. 6 Adverse effects to PGI2 infusion included sudden bradycardia, pallor and sweating, suggesting that the Bezold‐Jarisch reflex seen in animals in response to PGI2 may also occur in humans. 7 Neither increased sympathetic drive nor vagal withdrawal are likely causes of the tachycardia following PGI2 infusion.

Effect of epoprostenol (prostacyclin, PGI2) on cerebral blood flow in man.

“…The effects of PGI2 on blood pressure, pulse and the symptoms experienced by the subjects in the current study were similar to those found in previous work [12][13][14] and are discussed in more detail elsewhere. It seems likely that the headache frequently reported during PGI2 infusion is the result of vasodilation occurring in the external carotid circulation (as demonstrated by the facial flush), although the current results do not exclude the possibility that the headache results from changes in the calibre of larger intracranial vessels that are not reflected by alterations in cerebral perfusion.…”

Systolic time intervals: a review of the method in the non-invasive investigation of cardiac function in health, disease and clinical pharmacology

“…The effect of various prostaglandins on STI have also been studied. Prostacyclin infusion produced a dose-related decrease in diastolic blood pressure, PEP and QS2I (Warrington, Smith and O'Grady, 1980) and an increase in LVETI (Hassan et al, 1982).…”

Side effects occurring during administration of epoprostenol (prostacyclin, PGI2), in man.

“…The hypotension results from peripheral vasodilation (Eklund, et al, 1981) and the cause of the tachycardia is not yet clear (Hassan et al, 1982b). Although the hypotension is usually asymptomatic, it was listed as a side effect by Dowd et al.…”