Platelet phospholipase C activity in salt-dependent hypertension.
In spontaneously hypertensive rats (SHR), enhanced responsiveness of phospholipase C has been reported in various cells and tissues. In SHR and in some patients with essential hypertension particularly, the increased phospholipase C responsiveness of platelets has been described as involved in the hyperreactivity to thrombin. To determine the relation between such an enzymic abnormality and hypertension, the platelet phospholipase C activity was investigated in various models of experimental hypertension (i.e., in the Dahl salt-resistant and salt-sensitive strains inbred by John Rapp at Toledo, Ohio, SR/Jr and SS/Jr, respectively) fed either on a low or a high NaCl-containing diet, and in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In phosphorus-32-prelabeled platelets, phospholipase C was determined by measurement of the thrombin-induced [32P]phosphatidic acid formation; the labeling of the P47 protein with 32P was also measured. In parallel experiments, the platelet reactivity was assessed by measurement of the thrombin-induced serotonin release. Under thrombin (0.05-0.5 units/ml) stimulation, phospholipase C activity, [32P]P47 labeling, and serotonin release were significantly increased in SS/Jr rats fed a high NaCl diet compared with SS/Jr rats fed a low NaCl diet. NaCl-rich diet did not modify phospholipase C in SR/Jr rats. Platelet reactivity and phospholipase C responsiveness were also normal in DOCA-salt hypertensive rats compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Limon
I
I
Department of Pharmacology, Necker Hospital, Paris, France.
Blanc
J
J
Koutouzov
S
S
Knorr
A
A
Meyer
P
P
Marche
P
P
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D003900:Desoxycorticosterone; D004351:Drug Resistance; D006973:Hypertension / Q000097:blood* / Q000139:chemically induced; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000097:blood; D012965:Sodium Chloride; D013917:Thrombin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000097:blood*
D012701:Serotonin; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D010738:Type C Phospholipases; D013917:Thrombin