[Phospholipase C control of the hyperreactivity of platelets of the spontaneously hypertensive rat].
With respect to their biological responses the platelets of essentially hypertensive patients and of spontaneously hypertensive rats (SHR) are hyper-reactive to a variety of agonists. Platelet responses are mainly controlled by Ca2+ influx and/or mobilization and most of the platelet-activating substances act by stimulating the metabolism of phosphoinositides. Thus it is the hydrolysis of phosphatidylinositol 4,5-bisphosphate by phospholipase C that initiates platelet activation by thrombin. Assuming that an altered metabolism of phosphoinositides might participate in the hyper-reactivity of platelets from hypertensives, we studied phosphoinositide metabolism in washed platelets from SHR in relationship with the physiological cellular responses. This was carried out by measuring the variations in 32P-labeled lipids following incubation of platelets with 32P-orthophosphate. The results were compared with those obtained from washed platelets isolated from normotensive control rats of the Wistar-Kyoto strain (WKY). In unstimulated cells, both the rate and extent of 32P-incorporation into individual phospholipids were identical in SHR and WKY. This suggests that the pool size and basal turnover of phosphoinositides did not differ between the two strains. In contrast, early thrombin-induced lipid metabolism, when monitored as changes in 32P-phosphatidic acid (PA), was significantly higher in SHR than WKY and the extent of the difference was independent of the extracellular calcium concentration. Since following thrombin stimulation, 32P-PA formation likely reflects phospholipase C activity, our results suggest that this enzyme activity is enhanced in SHR platelets.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D010761:Phosphorus Radioisotopes / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000502:physiology*
D010761:Phosphorus Radioisotopes; D012701:Serotonin; D010738:Type C Phospholipases; D013917:Thrombin
Contrôle par la phospholipase C de l'hyper-réactivité des plaquettes du rat spontanément hypertendu (SHR).