Effects of calcium antagonists on intracerebral penetrating arterioles in rats

Abstract

✓ There is no direct information on the effect of calcium antagonists on intracerebral penetrating arterioles, which are responsible for a significant part of total cerebrovascular resistance. In a study on rats, the effects of four calcium antagonists (diltiazem, verapamil, nifedipine, and nimodipine) on isolated intracerebral penetrating arterioles with mean resting diameters (± standard error of the mean) of 52.3 ± 3.0 µm were investigated. Vessel diameters were monitored in vitro by means of a video microscope dimensional analyzer under constant transmural pressure (60 mm Hg) after cannulation. Each calcium antagonist produced maximal dilation of about 50% (diltiazem 46.4% ± 5.6%, verapamil 53.1% ± 6.0%, nifedipine 46.9% ± 6.1%, and nimodipine 47.1% ± 5.4%) with varied sensitivity (median effective dose (ED50): diltiazem 1.52 × 10−6 M, verapamil 1.08 × 10−7 M, nifedipine 8.65 × 10−9 M, and nimodipine 1.62 × 10−9 M). Dilation effects persisted for a significantly longer time after washout with calcium antagonists such as diltiazem (15.5 ± 1.8 minutes), nifedipine (19.0 ± 3.9 minutes), and nimodipine (30.0 ± 1.6 minutes) than after washout with adenosine (8.5 ± 1.0 minutes). It appeared that the magnitude of vasodilation was greater and the duration of dilation after washout longer in intracerebral penetrating arterioles than that reported for pial arterioles, although sensitivity to each calcium antagonist was quite similar to that reported for larger cerebral arteries. These data provide a possible explanation for the apparent disparity between clinical efficacy and angiographically determined vessel diameter when patients with cerebral vasospasm are treated with calcium antagonists. These agents may have a greater effect on intracerebral penetrating arterioles than on angiographically visible larger arteries.