PLATELET LIPOXYGENASE IN SPONTANEOUSLY HYPERTENSIVE RATS

We have previously reported that the nonselective lipoxygenase inhibit or phenidone is a potent hypotensive agent in the spontaneously hypert ensive rat (SHR). In the present study, we examined the relationship b etween production of platelet 12-hydroxyeicosatetraenoic acid (12-HETE ) and intraarterial blood pressure in SHR and Wistar-Kyoto rats (WKY) using both a cross-sectional analysis and an acute pharmacological int ervention. Basal generation rate of 12-HETE by platelets collected fro m 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). Sy stolic arterial pressure was positively related to platelet 12-HETE fo rmation rate when the entire rat population was considered (r=.70, P<. 001). The specific 12-lipoxygenase inhibitor cinnamyl-3,4-dihydroxycya nocinnamate induced lowering of both arterial blood pressure and plate let 12-lipoxygenase activity in SHR. At 15 mg/kg, cinnamyl-3,4-dihydro xycyanocinnamate elicited a marked hypotensive effect in SHR but not i n WKY. This reduction in arterial pressure was accompanied by an appro ximate 70% inhibition in platelet 12-HETE production rate. The return of high blood pressure to basal levels was associated with a significa nt rise in the production of platelet 12-HETE toward control values (b aseline, 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 bloo d pressure but had no effect on platelet 12-HETE generation rate. Thus , hypertension in SHR is linked to increased production rate of platel et 12-HETE. Acute blood pressure reduction attained during lipoxygenas e inhibition but nor 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 1 2-lipoxygenase activity in SHR may contribute to the maintenance of el evated arterial pressure in this strain.