Intracellular free Ca2+ and vasoconstriction determined simultaneously in the perfused rat tail artery.

To measure, simultaneously, intracellular free Ca2+ ([Ca2+]i) and vasoconstriction in a perfused vessel, we used the fluorescent Ca2+ indicator fura 2 with a dual-wavelength excitation method. One-centimeter-long segments of the caudal artery were dissected from 12-mo-old male Wistar rats. The endothelium was removed by gentle rubbing. The artery was mounted in a specially constructed spectrofluorometer cuvette, perfused with oxygenated physiological saline solution at 37 degrees C, and loaded by perfusion with fura 2 acetoxymethyl ester (5 microM) over a 90-min period. This paper is a description of the technique and the experiments that validate it as a useful method for examining Ca(2+)-related vascular reactivity in an intact perfused vessel.

Involvement of the renin-angiotensin system in ischemic damage and reperfusion arrhythmias in the isolated perfused rat heart.

We have investigated the contribution of the renin-angiotensin system to the damage caused by 40-min global ischemia in the isolated rat heart. A converting enzyme inhibitor, enalaprilat (70 nM), an angiotensin II receptor antagonist, compound 89 (2 microM), and an inhibitor of rat renin, CGP 44099A (20 nM), given before ischemia reduced the median duration of ventricular fibrillation on reperfusion to a similar extent (5.53, 5.72, and 5.14 min, respectively, compared to 13.98 min in the control group) but had no effect on creatine phosphokinase release (22.2 +/- 2.6, 22.1 +/- 6.8, and 24.1 +/- 3.6, IU/30 min, respectively, compared to 19.9 +/- 1.9 IU/30 min) or recovery or left ventricular developed pressure (67 +/- 6, 73 +/- 7 and 71 +/- 6%, respectively, compared to 66 +/- 3% after 30 min reperfusion). The increase in coronary resistance and left ventricular diastolic pressure on reperfusion was not affected by any of the agents. All three agents also tended to reduce the duration of ventricular fibrillation when given only on reperfusion. We conclude that angiotensinogen is present in the rat heart and it is converted to angiotensin I by a renin or a renin-like aspartic proteinase. The angiotensin I is converted to angiotensin II by converting enzyme. The angiotensin II formed is an important mediator of postreperfusion ventricular fibrillation in the isolated rat heart but does not contribute to the reduction in mechanical function produced by global ischemia in this preparation.