Platelets as a model for studying the action of antihypertensive drugs.
The action of different antihypertensive drugs on Ca2+ concentration in human platelets was studied under in vitro conditions and during the treatment of hypertensive persons. Several calcium antagonists (verapamil, nifedipine, and nicardipine) acted to block an increase of Ca2+ concentration in platelets which was induced by platelet activating factor (PAF), adenosine diphosphate, and U46619, the stable analog of thromboxane A2. All calcium antagonists suppressed dose-dependent calcium responses induced by each agonist. In a group of stable hypertensive patients, the basal Ca+ level in platelets was significantly higher than the level in mildly hypertensive or normotensive individuals. The induced increase in Ca2+ in the platelets of stable hypertensive patients was also higher, but this difference was not significant. Treatment of hypertensive patients with nifedipine for 3 weeks led to a decrease in calcium responses induced by all activators, but this decrease was significant only when PAF was used for platelet stimulation. Nifedipine added to platelets induced a nearly identical decrease in PAF-dependent calcium responses before and after therapy. Treatment with nifedipine in combination with furosemide and propranolol led to a more significant decrease in calcium responses than that expressed with monotherapy. In vitro experiments showed that furosemide has a calcium-blocking action on platelets, but that it is less expressed than the action of calcium antagonists. Low doses of propranolol did not influence calcium platelet responses, but high doses potentiated them slightly. A significant correlation was found between the percentage change in mean arterial pressure and in the PAF-induced responses with either monotherapy or combination drug therapy. Measurement of calcium responses before and after intravenous infusion of prostaglandin E2 showed that this procedure leads to a decrease in calcium responses that lasts for several days. The data suggest that platelets may be used as a model for investigating the action of drugs that influence calcium exchange when these drugs are administered chronically.
Menshikov MYu
Institute of Experimental Cardiology, USSR Academy of Medical Sciences, Moscow.
Avdonin
P V
PV
Kravchenko
A N
AN
Nekrasova
A A
AA
Mazaev
A V
AV
Shkhvatsabaya
I K
IK
D000328:Adult; D000634:Aminoquinolines; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000097:blood*; D004359:Drug Therapy, Combination; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology
D000634:Aminoquinolines; D000959:Antihypertensive Agents; C035738:Quin2-acetoxymethyl ester; D011433:Propranolol; D009543:Nifedipine; D002118:Calcium