Our results indicate that structural alterations of small cerebral vessels are present in hypertensive patients compared with normotensive individuals, similar to those previously observed in subcutaneous small arteries.

Objective: No data are presently available about changes in capillary density in the skeletal muscle and in the brain of spontaneously hypertensive rats (SHR) in relation to the development of hypertension.Design and methods: We have investigated 4 week-old and 12 week-old SHR and age-matched normotensive Wistar-Kyoto controls (WKY). Microvessel density (MVD) in the cerebral cortex and in a skeletal muscle were evaluated in sections stained for CD31. We also evaluated MVD in the dermal tissue of normotensive subjects and essential hypertensive patients. Subcutaneous small resistance arteries were dissected and mounted in a micromyograph and the media to lumen ratio (M/L) was measured.Results: A significant reduction in MVD in the skeletal muscle and in the brain of SHR was clearly observed at 12 weeks of age, after the development of hypertension, but not at 4 weeks of age (pre-hypertensive condition). In hypertensive patients a significant reduction in the dermal MVD and an inverse correlation between M/L and MVD was observed.Conclusions: Our results suggest that, in the brain and skeletal muscle of adult SHR after the development of hypertension, and in the derma of adult essential hypertensive patients microvascular rarefaction may occur.

Abstract-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 concentrationresponse 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. Key Words: endothelial function Ⅲ melatonin Ⅲ Pycnogenol oxidative stress R eactive oxygen species (ROS) are generated as byproducts of cellular respiration and other metabolic processes and may contribute to oxidative damage. 1,2 The ROS family includes several molecules that have divergent effects on cellular function, namely, regulation of cell growth and differentiation, modulation of extracellular matrix production and breakdown, inactivation of NO, and stimulation of protein kinases and proinflammatory genes. 3-5 Importantly, some of these actions are associated with pathological changes in cardiovascular tissues. 6 In cardiovascular disease, increased ROS production leads to endothelial dysfunction, increased vascular contractility, vascular smooth muscle cell growth and apoptosis, monocyte migration, lipid peroxidation, inflammation, and increased deposition of extracellular matrix proteins, all processes contributing to vascular damage. 7 ROS may be important in the development and maintenance of hypertension, in terms of excess production of oxidants, decreased NO bioavailability, and decreased antioxidant capacity in the vasculature and kidneys. 6,7 Hypertension may contribute to structural and functional al...

Our results suggest the presence of hypertrophic remodeling in sc small resistance arteries of CS, probably as a consequence of growth-promoting properties of circulating cortisol and/or increased vascular oxidative stress.

Our results indicate that subcutaneous small artery structure is related to MoR, possibly because an altered vascular structure may amplify BP changes or, vice versa, because a greater MoR may further damage peripheral vasculature.