Increased calcium uptake in vascular tissue, leading to elevated cytosolic free calcium, has been implicated in the pathophysiology of hypertension. This study examined the dose-dependent effect of deuterium oxide (5%, 10%, or 20% in drinking water) on systolic blood pressure, aortic calcium uptake, and platelet cytosolic free calcium in spontaneously hypertensive rats. Starting at age 8 weeks, spontaneously hypertensive rats were divided into four groups of six animals each. The drinking water of groups 1, 2, 3, and 4 was replaced by 100% water and 5%, 10%, and 20% deuterium oxide in water, respectively, for another 7 weeks. Ten Wistar-Kyoto rats, age 8 weeks, were given 100% water for the next 7 weeks. The usual increase in systolic blood pressure and the associated increase in aortic calcium uptake and platelet cytosolic free calcium in spontaneously hypertensive rats at age 15 weeks was lowered in a dose-dependent manner by deuterium oxide. Deuterium oxide also prevented renal vascular changes in spontaneously hypertensive rats. A minimum dose of 10% deuterium oxide was needed to completely prevent the development of hypertension, elevated aortic calcium uptake, platelet cytosolic free calcium, and renal vascular changes in spontaneously hypertensive rats. {Hypertension 1991;18:550-557) I n the last decade, much attention has been given to the hypothesis that cellular calcium metabolism is abnormal in various forms of hypertension. -6 Among the postulated defects are enhanced calcium influx across the cell membrane or reduced extrusion, or both, or sequestration of cytoplasmic calcium in association with elevated intracellular free calcium ([Ca 2+ ]i). Because of the relative availability of platelets and similarity of calcium-dependent contractile processes shared by platelets and vascular smooth muscle cells, 7 platelets have been used for analysis of the intracellular calcium. 24 It has also been shown to reduce the L-type calcium channel conductance in isolated guinea pig myocytes.25 D 2 O also depressed the contractile response of phenylephrine and KC1 in a dose-dependent manner in rat aortic rings. 26 We have shown recently that 25% D 2 O in drinking water normalizes blood pressure in Dahl salt-sensitive hypertensive rats and when given to prehypertensive SHR prevents the development of hypertension. Twenty-five percent D 2 O in drinking water also normalized elevated aortic calcium uptake in both SHR and Dahl salt-sensitive rats. However, it has no effect on blood pressure and vascular calcium uptake in normotensive rats. 27- 28 The objectives of the present study were to investigate the dose-dependent effect of 5%, 10%, and 20% D 2 O in drinking water on

This study examined the effect of moderate ethanol intake on systolic blood pressure, platelet cytosolic free calcium, aortic calcium, and rubidium-86 uptake in Wistar-Kyoto rats. Twelve Wistar-Kyoto rats, aged 6 weeks, were given 5% ethanol in drinking water the first week followed by 10% ethanol in drinking water for the next 6 weeks. Twelve control animals were given regular tap water. Systolic blood pressure in the ethanol-treated rats was significantly higher (p<0.05) than that in controls after 1 week and remained higher throughout the study. At 13 weeks of age, platelet cytosolic free calcium and calcium uptake by aortas were significantly higher (p< 0.001) in ethanol-treated animals as compared with those in controls. Ethanol intake did not affect aortic ouabain-sensitive 6 -8 However, the mechanisms by which ethanol intake elevates blood pressure is not known.Abnormal contractile activity of the vascular smooth muscle is considered to be one cause for the development of hypertension.9 The contractile activity of vascular smooth muscle is regulated by the level of intracellular free calcium ions ([Ca 2+ ]j). "12 It has been suggested that factors leading to an increased [Ca 2+ ]i within the vascular smooth muscle cell may be responsible for the increased contraction of the smooth muscle and the development of hypertension. Such factors may be an increased entry of calcium ions through the cell membrane via calcium channels or an increased release of calcium ions within the smooth muscle cells. Calcium influx through cell surface calcium channels is a major contributing factor to cytosolic free calcium. 1314 In the present study, we investigated the effect of an oral intake of 10% ethanol in drinking water on systolic blood pressure, platelet cytosolic free calcium and aortic calcium, and ^Rb* uptake in Wistar-Kyoto rats. Methods Animals, Diet, and Administration of EthanolMale WKY rats from Charles River, Quebec, Canada were used in this study. All rats were given standard rat chow throughout the study and had free access to water or water/ethanol mixture. At 6 weeks of age, rats were divided into two groups: a control group (12 rats) and an ethanol group (12 rats). Animals in the control group were given regular drinking water from the tap, and the ethanol group was given 5% vol/vol ethanol in tap water in the first week and 10% ethanol in tap water from the second through the

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This study examined the effect of 25% deuterium oxide in drinking water on systolic blood pressure, uptakes of calcium, and rubidium 86 by aortas of Dahl salt-sensitive rats on 0.4% (low) and 8% (high) sodium chloride (salt) diet. Twenty-four rats were divided into four groups. Groups I and II were on the low salt diet and groups HI and IV on the high salt diet from 6 weeks of age. Additionally, at 10 weeks of age groups I and III were placed on 100% water and groups II and IV on 25% deuterium oxide. At 14 weeks, systolic blood pressure, uptakes of calcium, and rubidium 86 by aortas were significantly higher (/?<0.01) in rats on the high salt diet as compared with those on the low salt diet Deuterium oxide intake normalized systolic blood pressure and aortic calcium uptake but not aortic rubidium 86 uptake in hypertensive rats on the high salt diet Deuterium oxide had no effect on blood pressure or aortic calcium uptake in rats on the low salt diet The parallel increase in systolic blood pressure and vascular calcium uptake suggests that increased calcium uptake mechanisms are associated with hypertension in salt-sensitive Dahl rats. Furthermore, deuterium oxide appears to normalize elevated blood pressure in salt-sensitive hypertensive rats by normalizing elevated vascular (aortic) calcium uptake. {Hypertension 1990;15:183-189) A bnormal contractile activity of the vascular smooth muscle is considered as one cause for the development of essential hypertension.1 The contractile activity of vascular smooth muscle is regulated by the levels of intracellular free Ca 2+ . 2 -4 It has been suggested that factors leading to an increased concentration of calcium ions within the vascular smooth muscle cell may be responsible for the increased contraction of the smooth muscle and the development of hypertension. Such factors may be an increased entry of calcium ions through the cell membrane, through either voltage-operated calcium channels or receptoroperated calcium channels or an increased release of calcium ions within the smooth muscle cells. Calcium influx through cell surface calcium channels is a major contributing factor to cytosolic free calcium. Calcium antagonists inhibit both the calcium influx through Ca 2+ channels and Ca 2+ release from the Ca 2+ -regulating sarcoplasmic reticulum and the Ca 2+ binding sites on the membrane of vascular smooth muscle. 6 Intra-arterial infusion of the calcium channel blockers verapamil and nifedipine produce marked vasodilation in humans.7 " 9 These calcium channel blockers also produce a greater relaxation response in blood vessels of spontaneously hypertensive rats compared with those of normotensive rats. 10Oral administration of these calcium channel blockers decrease blood pressure in hypertensive human subjects, 111 -12 as well as spontaneously hypertensive 13 and DahJ salt-sensitive hypertensive rats 14 but not in normotensive human subjects, normotensive WistarKyoto and Dahl normotensive rats.Deuterium oxide (D 2 O), a stable nonradioactive isotope of water has been...

Increased calcium uptake by vascular tissue, leading to elevated cytosolic calcium, has been implicated in the pathophysiology of hypertension. Heparin treatment of hypertensive rats has been known to lower blood pressure but its mechanism is not known. This study examined the effect of chronic heparin treatment on systolic blood pressure, aortic calcium and 87Rubidium (86Rb) uptake of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Starting at 12 weeks of age SHR and WKY rats were given either sodium heparin 300 units s.c. or equal amounts of saline once a day for a period of 6 weeks. At 18 weeks, systolic blood pressure, uptakes of calcium and 86Rb by aortae were significantly higher (p less than 0.01) in saline-treated SHR compared with heparin-treated SHR and WKY. Heparin treatment lowered the elevated calcium and 86Rb Uptake and blood pressure in SHR but had no effect on WKY. The parallel increase in systolic blood pressure and vascular calcium uptake suggests that increased calcium uptake mechanisms are associated with hypertension in SHR. Heparin appears to lower elevated blood pressure in SHR by lowering elevated vascular calcium uptake.