The action of diazoxide analogs on aortic reactivity in normotensive and spontaneously hypertensive rats

Diazoxide and four related 1,2,4-benzothiadiazines reduced the maximum responses to noradrenaline (NA) and KCl in aortic rings from normotensive and spontaneously hypertensive rats (SHR). These agents were more active against NA than against KCl responses, and more effective against either NA or KCl responses in aortae from hypertensive animals. Further studies with V (3-cyclopentenyl-6,7-dichloro-1,2,4 benzothiadiazine-1,1-dioxide), the most active member of the series, showed it to be significantly more effective against NA responses; when calcium was added to calcium-free solutions containing either NA or KCl, V was more effective in inhibiting either response in SHR aortae and was about 100 times more effective in inhibiting the calcium-NA responses. These data are consistent with previous findings that vascular smooth muscle from normotensive and SHR differs in sensitivity to diazoxide. However, the site(s) at which this difference is exhibited remains to be elucidated.