mortality/aging
• one-third of expected mice are produced from breeding heterozygotes
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cardiovascular system
• 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
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• in angiotensin II-treated mice
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• 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
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• 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
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• 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
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• 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
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• arteries exhibit a reduced increase in contraction induced by norepinephrine compared with wild-type arteries
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• 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
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muscle
• however, amiloride-sensitive base uptake is normal
• 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
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• arteries exhibit a reduced increase in contraction induced by norepinephrine compared with wild-type arteries
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• 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
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