title: Platelet lipoxygenase in spontaneously hypertensive rats.
abstract: We have previously reported that the nonselective lipoxygenase inhibitor phenidone is a potent hypotensive agent in the spontaneously hypertensive rat (SHR). In the present study, we examined the relationship between production of platelet 12-hydroxyeicosatetraenoic acid (12-HETE) and intra-arterial blood pressure in SHR and Wistar-Kyoto rats (WKY) using both a cross-sectional analysis and an acute pharmacological intervention. Basal generation rate of 12-HETE by platelets collected from the SHR was approximately 3.7-fold higher than in the WKY (0.86 +/- 0.24 versus 0.23 +/- 0.05 nmol/mL per 10 minutes, respectively; P < .01). Systolic arterial pressure was positively related to platelet 12-HETE formation rate when the entire rat population was considered (r = .70, P < .001). The specific 12-lipoxygenase inhibitor cinnamyl-3,4-dihydroxycyanocinnamate induced lowering of both arterial blood pressure and platelet 12-lipoxygenase activity in SHR. At 15 mg/kg, cinnamyl-3,4-dihydroxycyanocinnamate elicited a marked hypotensive effect in SHR but not in WKY. This reduction in arterial pressure was accompanied by an approximate 70% inhibition in platelet 12-HETE production rate. The return of high blood pressure to basal levels was associated with a significant rise in the production of platelet 12-HETE toward control values (baseline, 0.97 +/- 0.33 nmol/mL per 10 minutes; nadir of blood pressure, 0.19 +/- 0.03; resumption of basal pressure, 0.42 +/- 0.14). In contrast, captopril (15 mg/kg) induced a quantitatively similar decrease in blood pressure but had no effect on platelet 12-HETE generation rate. Thus, hypertension in SHR is linked to increased production rate of platelet 12-HETE. Acute blood pressure reduction attained during lipoxygenase inhibition but not by angiotensin converting enzyme inhibition leads to a concomitant reduction in the production of platelet 12-HETE. We speculate that since rat arterial tissue produces 12-HETE, increased 12-lipoxygenase activity in SHR may contribute to the maintenance of elevated arterial pressure in this strain.
authors.affiliation: Institute of Endocrinology, Tel Aviv-Elias Sourasky Medical Center, Ichilov Hospital, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Stern
authors.forename: E S
authors.initials: ES
authors.lastname: Kisch
authors.forename: E
authors.initials: E
authors.lastname: Knoll
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D002109:Caffeic Acids / Q000494:pharmacology; D003430:Cross-Sectional Studies; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood; D006973:Hypertension / Q000097:blood* / Q000503:physiopathology; D008084:Lipoxygenase / Q000097:blood*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR / Q000097:blood*; D011921:Rats, Inbred WKY / Q000097:blood
chemical_list: D002109:Caffeic Acids; D006893:Hydroxyeicosatetraenoic Acids; D016859:Lipoxygenase Inhibitors; C099255:cinnamyl-3,4-dihydroxycyanocinnamate; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D008084:Lipoxygenase