No abstract

SummaryIncubation of platelet-rich plasma (PRP) with ouabain, an inhibitor of sodium/potassium ATPase (Na+/K+ ATPase), induced a significant rise in basal platelet intracellular calcium concentration ([Ca2+]i) when measured using fura 2. Ouabain induced an enhanced aggregation response to low doses of collagen in both PRP and washed platelets loaded with aequorin. In aequorin loaded platelets this enhanced aggregation response was associated with an enhanced rise in [Ca2+]j such that the relationship between [Ca2+]i and aggregation was unchanged. As inhibition of plasma membrane Na+/K+ ATPase would lead to a raised intracellular sodium ion concentration ([Na+]i) the results suggest that in the platelet, [Na+]i can modulate [Ca2+]i and hence influence the response of platelets to stimuli such as collagen.

In concentrations above 20 p~, (k)-meptazinol produced a contraction of the guinea-pig isolated ileum and this effect was antagonized by atropine (0.01 to 0.3 p~) in a manner which was not competitive. Cooling the preparation to 15°C blocked the contractile action of meptazinol and of dimethylphenylpiperazinium (DMPP) but did not affect the action of carbachol. Twitch responses of the rat phrenic nerve-diaphragm preparation induced by indirect electrical stimulation in the presence of naloxone (20 nM) were potentiated by meptazinol (1 to 40 p~) which also reversed a partial blockade of the twitch induced by tubocurarine. Neither of these effects was seen in tissues which had been pretreated with the cholinesterase inhibitor BW284C51 (0.2 p~) though tetraethylammonium iodide 40 p~ was still able to enhance the responses to stimulation. In the presence of naloxone r j 20 nM electrically induced responses of the rat isolated rectum were abolished by cinchocaine (10 p~), partially blocked by atropine (0.1 to 0.4 VM) and potentiated by meptazinol (1 to 30 p~). The latter action was not seen when meptazinol was administered in the presence of BW284C51. It is concluded that the cholinergic action of meptazinol in these tissues is due to an indirect effect, probably involving inhibition of cholinesterase and that no evidence was seen of any ability to increase the release of acetylcholine itself.

SummaryThe relationship between blood pressure and platelet basal cytoplasmic calcium concentration ([Ca2+]i) and platelet sensitivity to aggregating agents in hypertension has been investigated in hypertensive patients and normotensive subjects. Ten severely hypertensive patients whose blood pressures were poorly controlled with metoprolol, were given calcium antagonist (either nifedipine or felodipine) as a second line agent. Venous blood samples were collected at each treatment phase for measurement, in whole blood, of platelet aggregation in response to ADP and collagen, and of basal [Ca2+]i using fura-2. Control of blood pressure by the combination of metroprolol and a calcium antagonist induced a significant decrease in median [Ca2+]i from 116 (76–181) to 73 (60–83) nM, which was similar to the median value of 70 (61–80) nM obtained in 14 normotensive subjects. Overall [Ca2+]i correlated with mean blood pressure (r = 0.51). Treatment of hypertension with calcium antagonist did not change the response of platelets to collagen or ADP. The results confirm that effective treatment of hypertension significantly reduced basal [Ca2+]i in platelets but raise doubts whether elevated basal [Ca2+]i is necessarily the sole mechanism by which the sensitivity of platelets to aggregatory agents is increased in hypertension.