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SUMMARY Vascular responses to calcium were studied in 14 genetically hypertensive (GH) rats of the New Zealand strain and 16 weight-and age-matched normotensive parent strain control rats under chloralose-pentobarbital anesthesia. Calcium (chloride or gluconate) in an isosmolar solution was infused intraarterially into the hindlimb vascular bed which was vascularly isolated, innervated, and pump-perfused (blood, 1 ml/min). Increases in limb plasma calcium concentrations up to 30 mEq/ liter decreased limb vascular resistance, with no evidence for vasoconstriction. In GH rats decreases in limb vascular resistance in response to increments in limb plasma calcium concentrations of 3.6 to 10.8 mEq/liter were significantly (p < 0.02) attenuated compared to age-matched controls. When responses in GH were compared to weight-matched controls, similar trends toward attenuation reached significance (p < 0.02) at Ca 2+ increments of 10.8 mEq/liter. In eight other GH rats, we measured total serum calcium concentrations and found them reduced (4.94 ± 0.08 mEq/liter), especially as compared to values in eight rats of an unrelated Wistar strain (5.42 ± 0.04 mEq/liter; p < 0.05). These experiments provide evidence that, over physiological ranges, calcium relaxes arteriolar smooth muscle in rats and that this vasod Nation is attenuated in genetically hypertensive rats. Thus, both the lower serum levels of calcium and the attenuated responses to calcium may contribute to the elevated peripheral vascular resistance and hypertension in these rats. (Hypertension 6: 647-653, 1984) KEY WORDS • vascular smooth muscle * serum calcium • serum proteins cell membrane ion transport • serum magnesium R ECENT evidence suggests abnormalities in calcium metabolism in spontaneously hypertensive rats of the Aoki-Okamoto strain (SHR), in rats with steroid hypertension, and also in patients with essential hypertension. Serum total and/ or ionized calcium is reported to be reduced, 1 ' 2 perhaps secondary to altered calcium binding to plasma proteins, decreased calcium intake, and/or increased renal calcium excretion. High calcium diets attenuate the hypertension while low calcium diets exacerbate it.3 -4

We have reported increases in ouabain-sensitive Rb+ uptake by freshly excised conduit arteries from volume-expanded Dahl salt-sensitive (S) rats and also from rats with chronic (4 to 6 weeks), benign (serum creatinine less than 1.4 mg%) one-kidney, one clip ( 1K1C ) hypertension on high NaCl intake. To assess in vivo arteriolar function in this latter model, and a role for putative circulating ouabain-like factors, we perfused the maximally vasodilated (nitroprusside, 0.015 mg/ml limb blood), vascularly isolated, innervated hindlimb vascular beds of chloralose-anesthetized, water- or saline-drinking 1K1C hypertensive rats with their own blood at 1 ml/min, and measured limb responses to i.a. norepinephrine 0.004 to 128 micrograms, before and during local infusion of ouabain (achieving 2.5 X 10(-5) M in limb blood). Complete dose-response curves in eight 1K1C hypertensive rats were steeper and higher than those in five uninephrectomized (1K) normotensive control rats. However, threshold and ED50 were unchanged. Thus, alterations in the curve in the hypertensive rats represented only structural vascular changes. Ouabain evoked a leftward shift of the dose-response curve in an additional 18 1K1C hypertensive rats and 13 1K normotensive controls. In the hypertensive rats as compared to the controls, there were trends for increases, rather than decreases, in the ouabain-induced shift of the curve. Shifts in 14 rats with chronic 2K1C hypertension did not differ from those in the 1K1C hypertensive rats. Together, these studies in chronic, presumably volume-expanded, low-renin hypertension unaccompanied by renal insufficiency provide no evidence for physiologically significant inotropic effects of circulating ouabain-like pump inhibitor.

SUMMARY We examined the relationship of intraocular pressure and the development of onekidney, one wrapped (perinephritic) hypertension in the dog. Conscious femoral arterial pressure (direct arterial puncture) and intraocular pressure (Schiotz tonometer) were measured weekly before and after the surgical induction of hypertension in 11 healthy male mongrel dogs and before and after unilateral nephrectomy in 15 normotensive control dogs. Preoperative mean arterial pressure (102 ± 5 vs 99 ± 8 [SD] mm Hg, hypertensive vs control dogs) and intraocular pressure (18.1 ± 2.5 ys 17.7 ±2.1 mm Hg, hypertensive vs control dogs) were similar in both groups. In normotensive control dogs, mean arterial pressure and intraocular pressure averaged over the postoperative period (4-8 weeks) did not differ significantly from preoperative values. In contrast, during the same period arterial pressure significantly increased and intraocular pressure significantly decreased in hypertensive dogs (arterial pressure, 163 ± 8 mm Hg; intraocular pressure, 11.9 ± 4.0 mm Hg; p < 0.001 for both values compared with corresponding values in control dogs). Intraocular pressure was inversely related to arterial pressure in hypertensive dogs (r = 0.56, p<0.01). These observations indicate that intraocular pressure decreases with the development of canine one-kidney, one wrapped hypertension. The mechanism of this decrease may be related to abnormalities in Na+,K + -adenosine triphosphatase activity found in this form of hypertension. (Hypertension 10: 152-156, 1987) KEY WORDS * blood pressure • aqueous humor • Na+,K+-adenosine triphosphatase T HERE is evidence for a circulating inhibitor of the Na + ,K + pump in dogs with chronic onekidney, one wrapped (1K1W; perinephritic) hypertension.1 -2 Because inhibition of Na + ,K + -adenosine triphosphatase (Na + ,K + -ATPase) has been associated with decreases in intraocular pressure, 34 we measured intraocular pressure during the development of perinephritic hypertension in dogs. Materials and MethodsOur techniques were similar to those we have used previously.15 Briefly, we trained healthy male mongrel pound dogs weighing between 20 and 32 kg and maintained on standard dog chow and water ad libitum