Summary
To determine whether blood-borne factors in hypertension accompanying early-stage kidney disease might be responsible for altered cellular calcium homeostasis, we measured changes in cytosolic calcium before and after incubating platelets in plasma ultrafiltrates from normotensive and hypertensive renal patients. With the use of the chelating agent quin 2, we found the free-calcium concentrations in platelets to be higher in the hypertensive than in the normotensive group. When both groups of participants were combined, a direct correlation was found between arterial pressure and cytosolic calcium. The cytosolic calcium concentration in platelets of normotensive renal patients increased after incubation with plasma from patients with untreated renal hypertension, but it was unchanged after incubation with plasma from normotensive subjects. These data indicate that the total cell burden of calcium is increased in platelets of hypertensive patients with earlystage renal disease, and that plasma from these patients contains a substance that is capable of increasing the cytosolic calcium concentration in platelets. If the plasma factor (or factors) acts not only on platelets, but also on vascular smooth muscle cells, it may contribute to the increased peripheral vascular resistance associated with hypertension of renal origin.
References
Astarie C, Levenson J, Simon A, Meyer P, Devynck MA (1989) Platelet cytosolic proton and free calcium concentrations in essential hypertension. J Hypertens 7:485–491
Aviv A, Livne A (1988) The Na+ /H+ antiport, cytosolic free calcium, and essential hypertension: a hypothesis. Am J Hypertens 1:410–413
Bachmann J, Schlüter H, Storkebaum W, Witzel H, Wessels F, Zidek W (1991) Effects of plasma from patients with essential hypertension on vascular resistance in the isolated perfused rat kidney. Clin Sci 80:17–23
Beretta-Piccoli C, Weidmann P, Schiffl H, Cottier C, Reubi FC (1982) Enhanced cardiovascular pressor reactivity to norepinephrine in mild renal parenchymal disease. Kidney Int 22:297–303
Blaustein MP (1977) Sodium ions, calcium ions, blood pressure regulation and hypertension. A reassessment and a hypothesis. Am J Physiol 231:C165-C173
Brickman AS, Nyby MD, von Hungen K, Eggena P, Tuck ML (1990) Calcitropic hormones, platelet calcium, and blood pressure in essential hypertension. Hypertension 16:515–522
Brod J, Bahlmann J, Cachovan M, Hubrich W, Hundeshagen H (1980) Pathogenese des renalen Hochdruckes. Klin Wochenschr 58:719–726
Brod J, Schaeffer J, Hengstenberg H, Kleinschmidt TG (1984) Investigations on the Na+, K+ pump in erythrocytes of patients with renal hypertension. Clin Sci 66:351–355
Chandra M, Rastogi R, Kumar A, Misra R, Shukla RN, Saxena AK, Shanker K (1990) Platelet ionic calcium and serum total calcium in essential hypertension. Indian J Exp Biol 28:96–97
Da Prada M, Zürcher G (1976) Simultaneous radioenzymatic determinations of plasma and tissue adrenaline, noradrenaline, and dopamine within femtomole range. Life Sci 19:1161–1174
Davidson WD, Sackner MA (1963) Simplification of the anthrone method for the determination of inulin in clearance studies. J Lab Clin Med 62:351–356
De Wardener HE, MacGregor GA (1980) Dahl's hypothesis that a saluretic substance may be responsible for a sustained rise in arterial pressure: its possible role in essential hypertension. Kidney Int 18:1–19
Erne P, Bolli P, Burgisser E, Bühler FR (1984) Correlation of platelet calcium with blood pressure: effect of antihypertensive therapy. N Engl J Med 310:1084–1088
Fröhlich ED, Tarazi RC, Dustan HP (1969) Re-examination of the hemodynamics of hypertension. Am J Med Sci 257:9–23
Grollman A, Krishnamurty VSR (1971) A new pressor agent of renal origin: its differentiation from renin and angiotensin. Am J Physiol 221:1499–1506
Haber E, Koerner T, Page KB, Kliman B, Purnode A (1969) Application of radioimmunoassay for the angiotensin I to the physiologic measurements of plasma renin activity in normal subjects. J Clin Endocrinol 29:1349–1355
Haller H, Oeney T, Huck U, Distler A, Philipp T (1989) Increased intracellular free calcium and sensitivity to angiotensin II in platelets of pre-eclamptic women. Am J Hypertens 2:238–243
Kilby MD, Broughton Pipkin F, Cockbill S, Heptinstall S, Symonds EM (1990) A cross-sectional study of basal platelet intracellular free calcium concentration in normotensive and hypertensive primigravid pregnancies. Clin Sci 78:75–80
Kramer HJ, Heppe M, Penning J, Knipowski J, Klingmüller D, Düsing R, Krück F (1985) Relation of endogenous digoxin-like immunoreactive activities to salt balance and renal function in man. Klin Wochenschr 62 [Suppl 3]:107–110
Land K, Kjeldsen SE, Od I, Westheim A, Hjermann I, Eide T, Gjesdal K (1988) Increased platelet and vascular smooth muscle reactivity to low dose adrenaline infusion in mild essential hypertension. J Hypertens 6:219–225
Le Quan Sang KH, Pernollet MG, Meyer P, Devynck MA (1990) Plasma digitalis-like activity and cytosolic calcium in essential hypertension. Am J Hypertens 3:171–175
Levenson J, Devynck MA, Pithois-Merli I, Le Quan Sang KH, Filitti V, Simon A (1990) Dynamic association between artery shear flow condition and platelet cytosolic free Ca2+ concentration in human hypertension. Clin Sci 79:613–618
Lindner A, Kenny M, Meacham AJ (1987) Effects of a circulating factor in patients with essential hypertension on intracellular free calcium in normal platelets. N Engl J Med 316:509–513
Marone C, Beretta-Piccoli C, Weidmann P (1980) Acute hypercalcemic hypertension in man: role of hemodynamics, catecholamines and renin. Kidney Int 20:92–96
Matsukawa S, Suzuki H, Jtaya Y, Nakajima S, Saruta T (1987) Short- and long-term efficacy of nifedipine in hypertensive patients with impaired renal function, with special reference to influencing factors. J Clin Hypertens 3:452–462
Michelakis AM, Mizukoshi H, Huang C, Murakami K, Inagami T (1975) Further studies on the existence of a sensitizing factor to pressure agents in hypertension. J Clin Endocrinol Metab 41:90–96
Mizukoshi H, Michelakis AM (1972) Evidence for the existence of a sensitizing factor to pressor agents in the plasma of hypertensive patients. J Clin Endocrinol Metab 34:1016–1024
Norris KC, Nemen MN, Kert CJ, Muallem S, Levine BS (1990) Basal and stimulated cytosolic platelet calcium in essential hypertension. J Hum Hypertens 4:110–112
Pritchard K, Raine AEG, Ashley CC, Castell LM, Somers V, Osborn C, Ledingham JGG, Conway J (1989) Correlation of blood pressure in normotensive and hypertensive individuals with platelet but not lymphocyte intracellular free calcium concentrations. Clin Sci 76:631–635
Schiffl H, Weidmann P, Beretta-Piccoli C, Cottier C, Sciler AJ, Ziegler WH (1982) Antihypertensive mechanism of the diuretic muzolimine in mild renal failure. Eur J Clin Pharmacol 23:215–220
Schiffl H (1989) Platelet cytosolic free calcium concentration in hypertension associated with early-stage kidney disease. Klin Wochenschr 67:676–681
Schiffl H (1990) Correlation of blood pressure in end-stage renal disease with platelet cytosolic free-calcium concentration. Klin Wochenschr 68:718–722
Tsien RY, Pozzan T, Rink TJ (1982) Calcium homeostasis in intact lymphocytes, cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator. J Cell Biol 94:325–334
Ueno H, Mikawa M, Takata M, Aasnoi H, Lida H, Sasayama S, Kagamimori S (1988) Does cytosolic free calcium concentration in platelets reflect tone and structural changes of resistance vessels? J Hypertens 6 [Suppl 4]:S255-S257
Zemel MB, Zemel PC, Berry S, Norman G, Kowalczyk C, Sokol RJ, Standly PR, Walsh MF, Sowers JR (1990) Altered platelet calcium metabolism as an early predictor of increased peripheral vascular resistance and preeclampsia in urban black women. N Engl J Med 323:434–438
Zidek W, Sachinidis A, Spieker C, Storkebaum W (1988) Effect of plasma from hypertensive subjects on Ca2+ transport in permeabilized human neutrohils. Clin Sci 74:53–56
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Schiffl, H. Modulation of platelet Ca2+ homeostasis by hypertensive plasma factor(s) derived from patients with early-stage renal disease. Klin Wochenschr 69, 917–923 (1991). https://doi.org/10.1007/BF01798539
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DOI: https://doi.org/10.1007/BF01798539