Effects of melatonin and Pycnogenol on small artery structure and function in spontaneously hypertensive rats.
It was suggested that oxidative stress has a key role in the development of endothelial dysfunction, as well as microvascular structural alterations. Therefore, we have investigated 2 substances with antioxidant properties: melatonin and Pycnogenol. We treated 7 spontaneously hypertensive rats (SHRs) with melatonin and 7 with Pycnogenol for 6 weeks. We compared results obtained with those observed in 7 SHRs and 7 Wistar-Kyoto normotensive control rats kept untreated. Mesenteric small resistance arteries were dissected and mounted on a wire myograph, and a concentration-response curve to acetylcholine was performed. Aortic contents of metalloproteinase 2, Bax, inducible NO synthase, and cyclooxygenase 2 were evaluated, together with the aortic content of total collagen and collagen subtypes and apoptosis rate. A small reduction in systolic blood pressure was observed. A significant improvement in mesenteric small resistance artery structure and endothelial function was observed in rats treated with Pycnogenol and melatonin. Total aortic collagen content was significantly greater in untreated SHRs compared with Wistar-Kyoto control rats, whereas a full normalization was observed in treated rats. Apoptosis rate was increased in the aortas of untreated SHRs compared with Wistar-Kyoto control rats; an even more pronounced increase was observed in treated rats. Bax and metalloproteinase 2 expressions changed accordingly. Cyclooxygenase 2 and inducible NO synthase were more expressed in the aortas of untreated SHRs compared with Wistar-Kyoto control rats; this pattern was normalized by both treatments. In conclusion, our data suggest that treatment with Pycnogenol and melatonin may protect the vasculature, partly independent of blood pressure reduction, probably through their antioxidant effects.
Rezzani
Rita
R
Clinica Medica, Department of Medical and Surgical Sciences, University of Brescia, Brescia, Italy.
Porteri
Enzo
E
De Ciuceis
Carolina
C
Bonomini
Francesca
F
Rodella
Luigi F
LF
Paiardi
Silvia
S
Boari
Gianluca E M
GE
Platto
Caterina
C
Pilu
Annamaria
A
Avanzi
Daniele
D
Rizzoni
Damiano
D
Agabiti Rosei
Enrico
E
D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D005419:Flavonoids / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D008638:Mesenteric Arteries / Q000187:drug effects / Q000473:pathology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010936:Plant Extracts; D011336:Probability; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013599:Systole / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D015415:Biomarkers; D005419:Flavonoids; D010936:Plant Extracts; C024070:pycnogenols; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D020778:Matrix Metalloproteinase 2; D008550:Melatonin