Selective and nonselective beta-blockade of the peripheral circulation.

The effects of selective beta 1- as compared to nonselective beta-adrenergic blocking drugs on the peripheral circulation have not been adequately investigated. Ten healthy subjects received placebo for 1 wk followed by 4 wk of either propranolol or metoprolol in equivalent but increasing doses each week. Subjects then crossed over to the other sequence of placebo and drug. Measurements of calf blood flow, mean blood pressure, and calculation of calf vascular resistance were obtained at rest, after three loads of supine exercise on a bicycle ergometer, and during isoproterenol infusion testing. At the doses chosen, both beta-adrenergic blocking drugs induced equivalent decreases in exercise heart rate. Metoprolol lowered resting and exercise mean blood pressure at most doses, whereas propranolol had less of an effect on this variable. Neither drug altered resting or exercise calf blood flow or vascular resistance. More isoproterenol was required to increase the heart rate and decrease the vascular resistance during treatment with propranolol than with metoprolol. We conclude that in normotensive subjects metoprolol is somewhat more effective than propranolol in lowering mean arterial pressure during exercise when the drugs are given at doses equivalent in effects on exercise heart rate. Neither drug has a deleterious effect on calf blood flow or vascular resistance. Despite this, a marked separation between the vascular beta 2-adrenergic-blocking effects of these drugs can be demonstrated with an isoproterenol infusion indicating beta 2-adrenergic-receptor sparing by metoprolol.

Fibrinogen synthesis stimulation by prostaglandin E1 and some other vasodilators.

Three-hour constant-rate intravenous infusion into rabbits of 1-3 mg prostaglandin E1 (PGE1) per kilogram markedly increased plasma fibrinogen 24 h later. 131I-labeled fibrinogen and model studies showed increased synthesis underlay this. Similar PGE1 doses lowered systolic blood pressure. Maintaining systolic blood pressure by infusing noradrenaline with the PGE1 did not alter plasma fibrinogen response to PGE1; plasma fibrinogen was unchanged by noradrenaline infusion. Regression equations relating plasma fibrinogen increment to PGE1 dose, plasma fibrinogen increment to dose and systolic blood pressure change, and systolic blood pressure change to dose are given as well as the constants relating plasma fibrinogen increment to dose using the Michaelis-Menten equation. Infusions of cyclic AMP, dibutyryl cyclic AMP, and cyclic GMP intravenously led to only small plasma fibrinogen increases. Daily intravenous infusions of PGE1 led to loss of both plasma fibrinogen and systolic blood pressure responses in two animals; a third animal showed only loss of the former and a fourth only loss of the latter response. PGE1 slightly enhanced the small plasma fibrinogen increase following intravenous bradykinin. Approximate arterial blood PGE1 concentrations resulting from the intravenous infusion of 1 mg mg PGE1 kg-1 3 h-1 are calculated. These are compared with measured values.