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(Hypertension. 1996;27:1149-1152.)
© 1996 American Heart Association, Inc.
Articles |
Platelet Lipoxygenase in Spontaneously Hypertensive Rats
From the Institute of Endocrinology, Tel Aviv–Elias Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv (Israel) University.
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.
Key Words: arachidonate 12-lipoxygenase • lipoxygenase • hydroxyeicosatetraenoic acids • rats, inbred SHR • blood pressure
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