[Changes in the inhibitory processes of platelet activation in the SHR rat].
A hyperreactivity to thrombin of platelets from spontaneously hypertensive rats (SHR) has been shown in vitro but no signs of platelet hyperactivation has been evidenced in vivo in these animals. Therefore, we have studied the effect of two inhibitory agents, PGE1 and magnesium, on platelet activation. The first drug is known to specifically act through adenylate cyclase stimulation, the second to have diffuse cellular effects as enzymatic cofactor. Blood of SHR and WKY adult animals was drawned by carotid catheterism. After isolation, platelets were loaded with 5-HT (either tritiated or not), then washed and incubated in a Hepes buffer, pH 7.4 with various concentrations of external calcium and magnesium, at 30 degrees C and with minimal stirring. Thrombin-induced platelet 5-HT secretion was evaluated, after preincubation in the presence of tritiated serotonin, in percentage of the initial load. Cyclic AMP content was measured by radioimmunoassay. Calcium influx was measured 30 seconds after thrombin addition by 45Ca incorporation. The inhibitory effect of PGE1 on 5-HT secretion is more important with SHR platelets than WKY ones, at 5 X 10(-8) and 10(-7)M. On the other hand, SHR platelets are less sensitive to inhibitory effect of external magnesium (1 to 10 mM). Between 10(-7) and 10(-6)M, PGE1 induces an increase of cAMP content, significantly more important in SHR, which persists in the presence of isobutylmethylxanthine (IBMX) 10(-5)M. Platelet reaction to thrombin is the more decreased as intracellular cAMP level before thrombin addition is enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)
Dard
B
B
U7 INSERM, Département de Pharmacologie, Hôpital Necker, Paris.
Baudouin-Legros
M
M
Meyer
P
P
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000097:blood / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology
D011458:Prostaglandins E; D012701:Serotonin; D000242:Cyclic AMP; D013917:Thrombin; D008274:Magnesium; D002118:Calcium
Altérations des processus inhibiteurs de l'activation plaquettaire chez le rat SHR.