Effects of pioglitazone on plasma insulin levels, systolic blood pressure and arterial reactivity were studied in spontaneously hypertensive (SH) rats, Chronic treatment of SH rats with pioglitazone decreased plasma insulin levels and blood pressure, Direct effects of pioglitazone on vascular reactivity were also studied in aortae and superior mesenteric arteries from SH rats, Pioglitazone markedly inhibited arginine vasopressin (AVP) and norepinephrine (NE) responses without affecting responses to potassium chloride (KCl), These data suggest that (a) antihypertensive effects of pioglitazone in SH rats may be mediated via a direct vasodepressor effect, and (b) vasodilation may be coupled to insulin sensitivity in SH rats.