Increased platelet aggregation and intracellular calcium in hypertensive patients: effects of cyclo-oxygenase blockade.

Increased platelet aggregation induced by ADP and arachidonic acid was observed in 12 patients with essential hypertension compared with 12 control subjects, but not after pretreatment with acetylsalicylic acid. The increase in intracellular calcium induced by ADP was also greater in the hypertensive patients, and again this difference disappeared after cyclo-oxygenase blockade. Urinary excretion of 2,3-dinor-thromboxane B2, the main metabolite of platelet thromboxane A2, was slightly, but not significantly increased in the hypertensive patients. These data suggest that thromboxane system activity is increased in the platelets of hypertensive patients.

Platelet intracellular free Ca2+ after incubation with plasma from hypertensive patients.

Variations in intracellular free calcium were measured in platelets from normal donors, incubated with plasma from hypertensive patients and from control subjects to test the hypothesis that a circulating factor might induce an increase in calcium concentration. Before incubation, plasma was heat-inactivated or ultrafiltered. Incubation both with heat-inactivated and ultrafiltered plasma failed to result in any significant modifications in intracellular free calcium. Similarly, no significant increase was observed after incubation with ouabain at concentrations ranging from 10(-7) to 10(-4) M. No significant differences were observed between platelets incubated with plasma from hypertensive as compared with control subjects. These findings are not consistent with the hypothesis that the increase in intracellular free calcium observed in platelets of hypertensive patients may be due to a plasma ouabain-like factor.

Intracellular free Ca2+ in platelets of essential hypertensive patients. Lack of correlation with clinical and laboratory data.

Platelet intracellular free Ca2+, [Ca2+]i, was found to be higher in 64 hypertensive patients than in 65 age- and sex-matched normotensive controls (142.7 +/- 3.8 nmol/l vs 126.6 +/- 2.4 nmol/l, M +/- SEM, respectively; P less than 0.001). No differences were observed in hypertensive patients in relation to age, duration of hypertension or severity of retinopathy, but a slight correlation was observed (r = 0.275, P less than 0.05) between platelet [Ca2+]i and systolic blood pressure. No correlations were found between platelet [Ca2+]i and plasma cholesterol, triglycerides, aldosterone or renin activity. These data appear to support the hypothesis that increased platelet [Ca2+]i in hypertensive patients is more likely to be related to a primary cellular abnormality than to activation by extrinsic humoral or vascular factors.

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

Intracellular free calcium, [Ca2+]i, 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 [Ca2+]i 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 less than 0.001). Epinephrine, norepinephrine, angiotensin II, and ouabain had no effect on platelet calcium, whereas thrombin induced a dose-dependent increase in [Ca2+]i in both the presence and absence of extracellular calcium. This [Ca2+]i increase in the presence of extracellular calcium, which depends mainly on calcium influx, was significantly higher (p less than 0.05) in platelets of hypertensive subjects at all thrombin concentrations (ranging from 0.025-0.1 U/ml), while the [Ca2+]i 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 [Ca2+]i 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.

Verapamil inhibits platelet aggregation by a calcium-independent mechanism.

We studied the inhibitory effects of the calcium channel blocker verapamil both on platelet aggregation and intracellular calcium [Ca2+]i in platelets loaded with a fluorescent indicator (quin 2). The inhibitory effects of verapamil on the platelet aggregation response to both thrombin and ionomycin were seen to be clearly dissociated from the verapamil-induced inhibition of the [Ca2+]i increase produced by these agonists. Verapamil-induced inhibition of platelet aggregation was also obtained when using the "calcium-independent" agonist phorbol-myristate acetate (PMA). It may be deduced that a calcium-independent mechanism plays a role in verapamil-induced inhibition of platelet aggregation. We postulate that this mechanism may operate via a protein-kinase C pathway.

Influence of cold plastic deformation on critical pitting potential of AISI 316 L and 304 L steels in an artificial physiological solution simulating the aggressiveness of the human body.

The effect of cold working on critical pitting potential of AISI 316 L and 304 L steels in a buffered physiological solution has been studied. In particular, the importance of deformation degree, orientation of the specimen surface to the deformation direction, and cold working temperature in lowering the critical pitting potential is shown.