title: Plant sterols and casein-derived tripeptides attenuate blood pressure increase in spontaneously hypertensive rats.
abstract: In this study, we investigated the synergistic effects of plant sterols (PS) and casein-derived tripeptides on arterial tone and blood pressure in experimental hypertension. We hypothesized that PS and tripeptides could have positive, synergistic effects on the development of hypertension and endothelial dysfunction in young spontaneously hypertensive rats (SHR). Six-week-old male SHR were divided into 3 groups to receive milk products containing PS, or PS with tripeptides, or a control containing no active components for 8 weeks. Systolic blood pressure (SBP) was measured weekly, and vascular reactivity measurements with isolated mesenteric arteries were performed at the end of the study. Biochemical measurements for several parameters were performed by enzyme-linked immunosorbent assay using plasma samples. Levels of angiotensin-converting enzyme 1, cyclooxygenase-2, endothelial nitric oxide synthase, and P-selectin messenger RNA expressions were determined from aortic tissue by real-time polymerase chain reaction. The study showed that long-term treatment with PS + tripeptides attenuated the development of hypertension in SHR (SBP, 187 ± 5 mm Hg vs 169 ± 4 mm Hg in control group; P < .01). Plant sterols alone did not affect SBP significantly. Endothelial dysfunction was observed in all SHR; however, treatment with PS resulted in poorer endothelium-dependent and nitric oxide-mediated relaxation compared with other groups. Aortic cyclooxygenase-2 and P-selectin were significantly down-regulated in PS and PS + tripeptides groups when compared with the control group. The expression of endothelial nitric oxide synthase was significantly lower in PS than in PS + tripeptides group. In conclusion, long-term treatment with PS has a slight but not significant antihypertensive effect. Plant sterols do not provide any beneficial effects on endothelial function in hypertensive rats; however, treatment with both PS and tripeptides showed mild anti-inflammatory effects.
authors.affiliation: Institute of Biomedicine, Pharmacology, University of Helsinki, 00014 Helsinki, Finland. pauliina.ehlers@helsinki.fi
authors.forename: Pauliina I
authors.initials: PI
authors.lastname: Ehlers
authors.forename: Anne S
authors.initials: AS
authors.lastname: Kivimäki
authors.forename: Aino
authors.initials: A
authors.lastname: Siltari
authors.forename: Anu M
authors.initials: AM
authors.lastname: Turpeinen
authors.forename: Riitta
authors.initials: R
authors.lastname: Korpela
authors.forename: Heikki
authors.initials: H
authors.lastname: Vapaatalo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002364:Caseins / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D010840:Phytosterols / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000893:Anti-Inflammatory Agents; D000959:Antihypertensive Agents; D002364:Caseins; D019007:P-Selectin; D010840:Phytosterols; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D007703:Peptidyl-Dipeptidase A