Pumpkin-seed oil modulates the effect of felodipine and captopril in spontaneously hypertensive rats

Natural products like pumpkin-seed oil (PSO) may modify the potency of the calcium antagonist felodipine (FEL) or angiotensin-converting enzyme inhibi tor (ACE-inhibitor), captopril (CPT) in modulating the biochemical derangem ent in blood, heart and kidney as well as blood pressure and heart rate of spontaneously hypertensive rats (SHR) were investigated. SHR were treated o rally with FEL at a dose of 0.45 mg kg(-1) body wt, or CPT at a dose of 9 m g kg(-1) body wt. once daily for 4 weeks. PSO was administered at a dose of 40 mg kg(-1) body wt. alone or with FEL or CPT in the previous respective dose regimen for the same period to SHR. This study showed that hypertensio n induced increments the content of malondialdehyde (MDA) by 55% and 38% as well as the activity of glutathione peroxidase (GSH-Px) by 26% and 23% in heart and kidney, respectively, accompanied by reductions in the activity o f myocardial superoxide dismutase (SOD) from 3.40 +/- 0.17 to 2.42 +/- 0.19 U mg protein(-1) and contents of glutathione (GSH) and protein thiols (PrS Hs) in different tissues of SHR as compared to normotensive rats. Treatment of SHR with FEL or CPT monotherapy or combined with PSO produced improveme nt in the measured free radical scavengers in the heart and kidney. Our res ults also showed that pretreatment of SHR with PSO for 4 weeks then i.v. ad ministration of FEL or CPT produced a significant beneficial hypotensive ac tion. The results were explained in the light of the antioxidant properties of PSO. Therefore, it is concluded that concomitant administration of FEL or CPT with natural antioxidants can yield a beneficial therapeutic effect and retard the progression of hypertension. (C) 2000 Academic Press.