Genetic A[T.sub.1A] receptor deficiency attenuates cold-induced hypertension

The aim of this study was to test our hypotheses that A[T.sub.1A] receptors play a role in the pathogenesis of cold-induced hypertension (CIH) and in the cold-induced increase in drinking responses to ANG II. Two groups of wild-type (WT) and two groups of A[T.sub.1A] receptor gene knockout (A[T.sub.1A]-KO) mice were used (6/ group). Blood pressures (BP) of the four groups were similar during the control period at room temperature (25[degrees]C). After the control period, one group of WT and one group of A[T.sub.1A]-KO mice were exposed to cold (5[degrees]C), while the remaining groups were kept at 25[degrees]C. BP of the cold-exposed WT group elevated significantly within 1 wk of exposure to cold and increased gradually to a maximum level by week 5. However, there was only a slight increase in BP of the cold-exposed A[T.sub.1A]-KO group. The maximal cold-induced increase in BP ([DELTA]BP) is significantly less in A[T.sub.1A]-KO group (11 [+ or -] 3 mmHg) than in WT group (49 [+ or -] 6 mmHg), indicating that A[T.sub.1A] receptor deficiency attenuates cold-induced elevation of BP. Interestingly, both WT and A[T.sub.1A]-KO mice developed cardiac and renal hypertrophy to the same extent. A[T.sub.1A]-KO caused a significant increase in urine and plasma levels of nitric oxide (NO), indicating that the renin-angiotensin system inhibits NO formation probably via A[T.sub.1A] receptors. Cold exposure inhibited endothelial NO synthase protein expressions and decreased urine and plasma levels of NO, which may be mediated partially by A[T.sub.1A] receptors. A[T.sub.1A]-KO completely abolished the cold-induced increase in drinking responses to ANG II. We conclude that 1) A[T.sub.1A] receptors play an essential role in the pathogenesis of CIH but not cardiac hypertrophy; 2) the role of A[T.sub.1A] receptors in CIH may be mediated partially by its inhibitory effect on the NO system; and 3) cold-induced increase in drinking response to ANG II is mediated by A[T.sub.1A] receptors. blood pressure; cardiac hypertrophy; mice; nitric oxide; endothelial nitric oxide synthase