Since chronic norepinephrine administration reduces the maximal force of contraction, we asked if catecholamine release differs in pendrin null mice and wild type mice. Thus, urinary epinephrine and norepinephrine were measured in wildtype and pendrin null mice. As shown, 24 hr urinary excretion of epinephrine and norepinephrine was similar in wildtype and pendrin knockout mice. Thus, the increase in aortic contractility/cross sectional area observed with pendrin gene DEL-22379 ablation cannot be explained by changes in basal levels of catecholamine production. Following 7 days of the NaCl-replete, gelled diet employed in this study, the present and previous UK-371804 studies have shown that mean arterial blood pressure is 5 to 9 mm Hg lower in pendrin null relative to wild type mice when measured by telemetry. Whereas we observed mean arterial blood pressures of 116 to 122 mm Hg in wild type mice, MAP was in the range of 113 to 116 mm Hg in pendrin null mice. Whether the fall in blood pressure observed with pendrin gene ablation is accompanied by changes in vascular tone has been unexplored. We hypothesized that since blood pressure is reduced in pendrin null mice, vascular reactivity and the contractile response should be attenuated in the mutant mice. Our results indicate that pendrin gene ablation increases contractile force normalized to cross sectional area in response to phenylephrine and angiotensin II. However, the sensitivity to contractile agents such as phenylephrine or KCl is unaffected. Since pendrin mRNA and protein are not detectable in conduit vessels, pendrin gene ablation alters aorta contractility through an indirect and possibly systemic effect of pendrin gene ablation. Since thyroid hormone, aldosterone and cortisol levels are the same in pendrin null and wild type mice under the conditions of the present study, the differences in contractility observed in the present study cannot be explained by changes in the production of these hormones. However, under the treatment conditions employed in the present study, circulating renin concentration is two-fold higher in pendrin null relative than in wild type mice.