All Phenotypes Slc4a7<Gt(40G1)Cmhd> MGI Mouse

preweaning lethality, incomplete penetrance ( J:189470 )

• one-third of expected mice are produced from breeding heterozygotes

abnormal heart rate ( J:189470 )

• L-NAME-induced decrease in heart rate is reduced compared to in wild-type mice

• after administration of Y-27632, mice exhibit attenuated increase in heart rate compared with wild-type mice

increased heart rate ( J:189470 )

• in angiotensin II-treated mice

abnormal systemic arterial blood pressure ( J:189470 )

• L-NAME-induced increase in mean arterial blood pressure is blunted compared to in wild-type mice

• mice are resistant to hypertension induced by angiotensin-II infusion compared with wild-type mice

• after administration of Y-27632 with or without L-NAME or angiotensin-II treatment, mice exhibit reduced change in mean arterial pressure compared with wild-type mice

increased mean systemic arterial blood pressure ( J:189470 )

• L-NAME-induced increase in mean arterial blood pressure is blunted compared to in wild-type mice

• mice are resistant to hypertension induced by angiotensin-II infusion compared with wild-type mice

• after administration of Y-27632 with or without L-NAME or angiotensin-II treatment, mice exhibit reduced change in mean arterial pressure compared with wild-type mice

abnormal vascular endothelial cell physiology ( J:189470 )

• steady-state intracellular pH is lower than in wild-type mice

• in the absence of carbon dioxide and bicarbonate, the rate and extent of acidification on sodium removal and the rate of intracellular pH recovery on sodium re-addition is increased compared to in wild-type mice

• endothelial nitric oxide production is reduced compared with wild-type arteries

• arteries exhibit impaired resting and/or norepinephrine-induced nitric oxide production compared with wild-type arteries

• arteries exhibit reduced rho-kinase-dependent calcium sensitivity compared with wild-type arteries

• however, intracellular pH is normal in the absence of carbon dioxide and bicarbonate

abnormal vascular smooth muscle physiology ( J:189470 )

• sodium- and bicarbonate-dependent base uptake is abolished in arteries

• vascular smooth muscle cells exhibit larger sodium/hydrogen-exchange activity compared with wild-type cells

• in the presence of carbon dioxide and bicarbonate, steady-state intracellular pH in vascular smooth muscle cells is lower than in wild-type mice

• removal of carbon dioxide and bicarbonate fails to acidify vascular smooth muscle cells

• without carbon dioxide and bicarbonate, cariporide causes a larger decrease in steady-state intracellular pH in arteries compared with wild-type cells

• however, amiloride-sensitive base uptake is normal

abnormal vasoconstriction ( J:189470 )

• arteries exhibit a reduced increase in contraction induced by norepinephrine compared with wild-type arteries

decreased vasodilation ( J:189470 )

• in response to acetylcholine in arteries in the presence of carbon dioxide and bicarbonate

• L-NAME-sensitive relaxation in arteries is reduced in the presence of carbon dioxide and bicarbonate

• however, arteries exhibit normal L-NAME-insensitive, bicarbonate-free, L-NAME-insensitive/bicarbonate-free and L-NAME-sensitive/bicarbonate-free relaxation

• however, relaxation response to NO-donor S-nitroso-N-acetylpenicillamine is normal