Deuterium oxide normalizes blood pressure and vascular calcium uptake in Dahl salt-sensitive hypertensive rats.

Abstract

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...

Deuterium oxide prevents hypertension and elevated cytosolic calcium in hypertensive rats.

“…These in vitro effects of D 2 0 were concentration dependent. 27 ' 28 In experiments using guinea pig ventricular myocytes, others have reported that isotopic substitution of deuterium for hydrogen may affect cell surface Ca 2+ channels. 25 The antihypertensive effects of D 2 O may be the result of increased blockage of calcium channels by bound deuterium ions.…”

“…- 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 …”

Platelet-free calcium and vascular calcium uptake in ethanol-induced hypertensive rats.

“…Calcium uptake by thoracic aortic tissues was measured as described previously, 20 - 21 and thoracic aortas were excised and dissected free of connective tissue in a constantly oxygenated HEPES buffer (pH 7.4) solution containing: 150 mM NaCl, 4.5 mM KC1, 10 mM D-glucose, 5 mM HEPES, 1.5 mM CaCl 2 , and 1 mM MgCl 2 . Aortas were then cut into 2-3-mm long segments.…”

“…Under these conditions, efflux of intracellular calcium is prevented and only the extracellular calcium is effectively washed away. 20 The tissues were then blotted, wet weights were measured and transferred to counting vials containing 100 fil H 2 O and 1 ml Protosol (New England Nuclear, Boston, Massachusetts, USA), and then were placed in a water bath for 2 hours at 60°-70°C. After digestion, 100 y\ glacial acetic acid was added to each vial followed by 10 ml liquid scintillation fluid (BDH Chemicals, Toronto, Canada), and the solution was counted in a Beckman liquid scintillation counter (Beckman Instruments, Fullerton, Calif. 86 Rb + uptake in vitro in thoracic aortic rings by an essentially similar method as described previously.…”

“…After digestion, 100 y\ glacial acetic acid was added to each vial followed by 10 ml liquid scintillation fluid (BDH Chemicals, Toronto, Canada), and the solution was counted in a Beckman liquid scintillation counter (Beckman Instruments, Fullerton, Calif. 86 Rb + uptake in vitro in thoracic aortic rings by an essentially similar method as described previously. 20 After an equilibration period of 2 hours subsequent to tissue excision, aortic rings (in tissue holders) were incubated in 5 ml of constantly oxygenated HEPES buffer containing 86 Rb + (2-10 /xCi/ml) for 30 minutes at 37°C in a constantly shaking water bath. After this period, tissues were placed in icecold (2°C) unlabeled buffer for 2 minutes to remove the radioisotope in the extracellular compartment.…”