Diabetics have a higher risk of developing cerebral vasospasms (CVSP) than nondiabetics. The addition of the ryanodine receptor (RyR) blocker dantrolene to standard therapies reduces vasospasms in nondiabetics. Whether diabetics with CVSP also benefit from this drug, however, is unknown. We evaluated the effects of a 30 min incubation with dantrolene (50 μM), nimodipine (50 nM), and both drugs in combination, on phenylephrine- (PHE-) induced contraction and on acetylcholine- (ACh-) induced relaxation in aortic rings from streptozotocin (STZ) diabetic rats. Age-matched, nondiabetic rats served as controls. The oxidative stress markers malondialdehyde (MDA) and 4-hydroxyalkenal (4-HAE) were also evaluated in the presence and absence of dantrolene and nimodipine. The combination of these two drugs acted synergistically to reduce the PHE-induced contraction by 80% in both diabetics and controls. In contrast, it increased the Emax value for ACh-induced relaxation (from 56.46 ± 5.14% to 96.21 ± 7.50%; n = 6, P < 0.05), and it decreased MDA + 4-HAE values in diabetic rats only. These results suggest that the combination of dantrolene and nimodipine benefits both diabetics and nondiabetics by decreasing arterial tone synergistically.

Whereas atorvastatin does not reverse ventricular dilatation, it does have a positive hemodynamic effect on the CV system of diabetic rats. This hemodynamic benefit is independent of cholesterol levels, and is observed concomitantly with reduced oxidative stress, vascular remodeling, and improved endothelial function. Together, these results suggest that atorvastatin decreases the workload on the heart and improves systolic performance in type 1 diabetic rats by reducing oxidative stress, vascular tone, and systemic vascular resistance.

AV, SV, and PV are equally effective in improving CV performance in diabetic rats. All tree statins decreased media thickness, perivascular fibrosis, and both MDA and 4-HAE in the aortas of diabetic rats, without affecting eNOS and iNOS protein levels. The observed hemodynamic benefits are cholesterol-independent. These benefits appear to be secondary to the improved endothelial function, and to the reduced vascular tone and remodeling that result from decreased oxidative stress.

These results suggest that hyperglycaemia modifies CV responses to induction anaesthetics.

Recent evidence suggests that statins improve the status of patients with coronary artery disease not only by reducing cholesterol levels, but also by acting at the level of the endothelium-smooth muscle unit. Previous results from our laboratory showed that these drugs interact with the vascular wall by partially inhibiting calcium-dependent, agonist-induced contractions in rat aortas. To evaluate whether this effect is also extended to the coronary vasculature, we assessed the effect of statins on serotonin (5-HT) induced contractions of left and right coronary arteries of swine. Concentration-response curves for the 5-HT-induced contractions (from 0.1 nmol/l to 100 µmol/l) were calculated on rings from both coronaries in the presence and absence of either (5 µmol/l) pravastatin, mevastatin, simvastatin, lovastatin, or atorvastatin. After a 45-min incubation period, all statins significantly reduced the E_max for the 5-HT-induced contractions, ranging from 51.9 ± 1.9% (simvastatin) to 15.9 ± 2.0% (pravastatin) in the left coronary artery and from 48.8 ± 2.0% (simvastatin) to 17.8 ± 2.5% (pravastatin) in the right coronary artery. The EC₅₀ values for the 5-HT-induced contractions were 0.150 ± 0.005 µmol/l for the left coronary artery and 0.171 ± 0.010 µmol/l for the right coronary artery. These values significantly changed after incubation with statins, ranging from 1.240 ± 0.101 µmol/l (for simvastatin) to 0.081± 0.008 µmol/l (for pravastatin) in the left coronary artery and from 1.410 ± 0.075 µmol/l (for simvastatin) to 0.084 ± 0.008 µmol/l (for pravastatin) in the right coronary artery. This evidence supports the possibility that, beyond their lipid-lowering properties, statins may provide a beneficial effect in atherosclerotic patients by reducing the tone in the coronary vasculature, facilitating blood flow to the myocardium.