Dantrolene and Nimodipine Reduce Arterial Tone Synergistically in Aortic Rings from Type‐1 Diabetic Rats

Diabetic patients have a high risk of developing cerebral vasospasms (CVSP). The current treatment of this condition is similar for diabetics and non‐diabetics, and includes the use of nimodipine and other calcium channel antagonists to reduce vasoconstriction. Concomitant administration of the ryanodine receptor (RyR) blocker dantrolene with these antagonists may be beneficial to diabetic patients, knowing that this combination reduces vasoconstriction in non‐diabetic patients. In this study, we evaluated the effects of dantrolene (50 μM), nimodipine (50 nM), and both drugs in combination, on the phenylephrine (PHE)‐induced contraction of aortic rings from streptozotocin (STZ)‐induced Type‐1 diabetic rats. Age‐matched non‐diabetic rats were used as controls (CT). PHE‐induced concentration response curves from 0.1 nM to 10 μM were performed on aortic rings in the presence and absence of dantrolene, nimodipine, or their combination. After a 30‐minute incubation period, the PHE‐induced contraction was reduced to the same percentages in diabetic and non‐diabetic rats by dantrolene (37 %; N=5, P<0.05) and nimodipine (about 50%; N=5, P<0.050). In contrast, the combination of these drugs reduced the PHE‐induced contraction by 81% in CT, but only by 69% in diabetic rats. In addition, endothelium‐independent relaxation with 10 μM sodium nitroprusside (SNP) was not affected by dantrolene or nimodipine in either diabetic or CT rats. Our results suggest that the combination of dantrolene and nimodipine may have beneficial effects in both diabetics and non‐diabetics with CVSP by decreasing arterial tone more than either drug alone. Supported by RCMI Grant G12‐RR03051. Support or Funding Information Supported by RCMI Grant G12‐RR03051.