Bromolasalocid (Ro 20-0006) antihypertensive ionophore.

Bromolasalocid (Ro 20-0006) is a calcium ionophore with antihypertensive activity that does not belong to any known class of antihypertensive agents. Bromolasalocid produces a relatively flat systolic blood pressure dose-response effect in the spontaneously hypertensive rat. An intensive cardiovascular evaluation of bromolasalocid at the highest dose used in the dose-response study showed full hemodynamic compensation; there was a significant decrease in both mean arterial blood pressure and peripheral resistance without a significant decrease in cardiac index. The antihypertensive action of bromolasalocid lasts many days after termination of dosing. Bromolasalocid is specifically antihypertensive and does not decrease arterial blood pressure in normotensive animals or in animal models of hypertensive cardiovascular disease with normal pulse pressures. Bromolasalocid is not a vasodilator and appears to mediate its antihypertensive action by restoring compliance of the large conduit arteries. Both the derived arterial compliance index and the blood pressure-pressor response to the carotid occlusion reflex are enhanced in the dog perinephritis model of hypertensive cardiovascular disease treated with bromolasalocid. Bromolasalocid appears to reverse the damage to cardiovascular tissue caused by prolonged hypertension via an action on calcium perturbations in large artery smooth muscle cells.

An improved signal processor for the ultrasonic dimension gauge.

The flip-flop producing a pulse proportional to the transit time of an ultrasonic burst between two piezoelectric crystals was often reset by transmission artefacts in sonomicrometers. A design improvement was made. The insertion of two monostable vibrators and one nand gate corrected the resetting caused by transmission artefacts. The new design produced a flip-flop pulse that was proportional to the transit time of the ultrasonic burst through the aorta. Ascending aortic diameter was monitored in unanaesthetised dogs for 6 to 8 weeks using the new design.

The cardiovascular pharmacology of the antibiotic ionophore Ro 2-2985 (X537A).

Ro 2-2985 increased mean arterial blood pressure in both the venous bypass preparation and the intact animal; however, total peripheral resistance increased in the venous bypass preparation with a constant cardiac output but decreased in the intact animal with an increase in cardiac output. These observations indicate a drug-related increase in the distensibility of the aorta at the same arterial pressure. In vivo ventricular function curves were shifted to the left indicating enhanced myocardial performance with the translocation of large volumes of blood to the central circulation since total body venous compliance was significantly decreased. Beta adrenergic blocking doses of propranolol blocked the positive inotropic effect of Ro 2-2985 while myocardial depression produced by toxic doses of propranolol was reversed. This observation suggests several mechanisms for the Ro 2-2985 metabolic mediation of myocardial muscle contraction. The cardiovascular effects produced by Ro 2-2985 were accompanied by a marked polycythemia and a decrease in plasma volume without a change in total circulating blood volume, while blood glucose values showed a nonsignificant increase. Ro 2-2985 produced a marked increase in cardiac output. The increase in myocardial performance appears to be complex since myocardial force of contraction, dT/dt, dP/dt:P40 and Vmax were all increased. RO 2-2985 increased coronary flow without an increase in resistance. There were no significant increases in myocardial arteriovenous glucose, lactate, K+, Ca++, Na+ or Cl.

Effects of L-dopa on myocardial contractile force: a reappraisal.

The apparent decrease in myocardial force of contraction observed after L-dopa, 10 mg/kg i.v., is artifactual since the maximum rate of left venticular isovolumic pressure rise (dP/dt) remains elevated. The apparent decrease is due to shrinkage in heart size secondary to venous "pooling". The decrease in contractile force parallels a decrease in cardiac output. A peripheral decarboxylase inhibitor and L-dopa produce a decrease in both contractile force and dP/dt. Strain gauge arch recordings may produce false-positive data during marked venous pooling.