Increased basal and thrombin-induced free calcium in platelets of essential hypertensive patients.

Abstract

SUMMARY Intracellular free calcium, [Ca 2 + ],, was studied in platelets of essential hypertensive subjects and normotensive controls under basal conditions and after stimulation with epinephrine, norepinephrine, angiotensin II, ouabain, and thrombin, using the fluorescent calcium indicator quin 2. Basal [Ca 2+ ], was significantly higher in hypertensive subjects (n = 32) than in normotensive controls (n = 30; 167.4 ± 5.0 vs 143.2 ± 3.1 nmol/L; p<0.001). Epinephrine, norepinephrine, angiotensin II, and ouabain had no effect on platelet calcium, whereas thrombin induced a dose-dependent increase in [Ca 2+ ]| in both the presence and absence of extracellular calcium. This [Ca 2+ ]| increase in the presence of extracellular calcium, which depends mainly on calcium influx, was significantly higher (p<0.05) in platelets of hypertensive subjects at all thrombin concentrations (ranging from 0.025-0.1 U/ml), while the [Ca 2+ ]| increase in the absence of extracellular calcium, which depends only on release from intracellular stores, was similar in hypertensive subjects and controls. These results suggest that, in essential hypertension, there is not only increased platelet resting [Ca 2+ ]| but also an increase in agonist-mediated calcium influx, which appears to indicate a cell membrane abnormality in the platelets of subjects with essential hypertension.

Abnormal platelet Ca2+handling accompanied by increased cytosolic free Mg2+in essential hypertension

“…In the present study, the basal [Ca 2ϩ ] i in platelets was elevated in hypertensive subjects, confirming most previous results (5,8,11,16,30). However, there was a considerable overlap in distribution between hypertensives and normotensives.…”

“…Platelets are often used in the study of cellular cation metabolism in hypertension, because they are readily available for study and are thought to share a number of features with vascular smooth muscle cells (20). Most investigators have reported that basal levels of cytosolic free Ca 2ϩ concentration ([Ca 2ϩ ] i ) are higher in human subjects with essential hypertension than in normotensive subjects (5,8,11,16,30) …”

Free cytosolic calcium in renal proximal tubules from the spontaneously hypertensive rat.

“…This issue is supported by the lack of a significant effect of ouabain on [Ca 2+ ], when added in vitro to our preparation of renal proximal tubules (see Figure 3). This finding is in agreement with other studies in cultured renal epithelial cells, 22 -47 toad urinary bladder, 28 and platelets, 48 although contrary evidence has been presented in renal cells. 49 The lack of effect of ouabain on [Ca 2+ ], in our preparation of renal proximal tubules is in contrast with the marked increase caused by removal of external Na + (J. Llibre, C. Gutterman, and D.C. Batlle, unpublished observation, 1988 50 and strophanthidin, another cardiotonic steroid, has been shown to increase contractile tension in small rings of rat aorta, suggesting increased Ca 2+ delivery to the contractile apparatus.…”

Cytosolic free calcium of aorta in hypertensive rats. Chronic inhibition of angiotensin converting enzyme.

“…A large body of evidence has indicated that [Ca 2+ ], levels in platelet or other blood cells are increased in SHR and hypertensive patients. 2 - 5 However, whether [Ca 2+ ], in VSMC is increased in genetic hypertension is controversial. 6 ' pared with age-matched normotensive Wistar-Kyoto (WKY) rats.…”