| Type | MGI:General | Description | anesthetized homozygous mutant mice were strongly hypertensive: their mean aortic blood pressure was 135 ± 3 mmHg, compared with 84 ± 6 mmHg for isogenic wild-type control mice; hypertension was confirmed in unanesthetized freely moving mice transthoracic echocardiography of 6-month-old homozygous mutant mice revealed no significant reduction in systolic contractile function or evidence of hypertrophy relative to wild-type homozygous mutant mice displayed small increases in blood pressure in response to a maximal dose of angiotensin II or phenylephrine, thus eliminating hypertrophy of the resistance vasculature as the cause of the hypertensive phenotype homozygous mutant mice displayed significantly prolonged vasoconstrictor responses of the peripheral resistance vasculature in vivo and of aortic vascular smooth muscle cells in vitro; by prolonging the rate at which vasoconstrictor signaling terminates, the mutation is proposed to increase the duration of contraction by the resistance vasculature, thus elevating blood pressure in support of this hypothesis, the mutant hypertensive phenotype was reversed within minutes following either blockade of angiotensin II production with an ACE inhibitor or antagonism of AT1 receptors; also, the rate of blood pressure decline in homozygous mutant mice infused with an AT1 antagonist was slower than that in similarly treated wild-type littermates |
