Nutraceuticals and blood pressure control: a European Society of Hypertension position document.

: High-normal blood pressure (BP) is associated with an increased risk of cardiovascular disease, however the cost-benefit ratio of the use of antihypertensive treatment in these patients is not yet clear. Some dietary components and natural products seems to be able to significantly lower BP without significant side effects. The aim of this position document is to highlight which of these products have the most clinically significant antihypertensive action and wheter they could be suggested to patients with high-normal BP. Among foods, beetroot juice has the most covincing evidence of antihypertensive effect. Antioxidant-rich beverages (teas, coffee) could be considered. Among nutrients, magnesium, potassium and vitamin C supplements could improve BP. Among nonnutrient-nutraceuticals, soy isoflavones could be suggested in perimenopausal women, resveratrol in insulin-resistant patients, melatonin in study participants with night hypertension. In any case, the nutracutical approach has never to substitute the drug treatment, when needed.

Effect of antihypertensive treatments on insulin signalling in lympho-monocytes of essential hypertensive patients: a pilot study.

It was previously demonstrated that metabolic syndrome in humans is associated with an impairment of insulin signalling in circulating mononuclear cells. At least in animal models of hypertension, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) may correct alterations of insulin signalling in the skeletal muscle. In the first study, we investigated the effects of a 3-month treatment with an ARB with additional PPARγ agonist activity, telmisartan, or with a dihydropyridine calcium channel blocker, nifedipine, on insulin signalling in patients with mild-moderate essential hypertension. Insulin signalling was evaluated in mononuclear cells by isolating them through Ficoll-Paque density gradient centrifugation and protein analysis by Western Blot. An increased expression of mTOR and of phosphorylated (active) mTOR (p-mTOR) was observed in patients treated with telmisartan, but not in those treated with nifedipine, while both treatments increased the cellular expression of glucose transporter type 4 (GLUT-4). We also investigated the effects of antihypertensive treatment with two drug combinations on insulin signalling and oxidative stress. Twenty essential hypertensive patients were included in the study and treated for 4 weeks with lercanidipine. Then they were treated for 6 months with lercanidipine + enalapril or lercanidipine + hydrochlorothiazide. An increased expression of insulin receptor, GLUT-4 and an increased activation of p70S6K1 were observed during treatment with lercanidipine + enalapril but not with lercanidipine + hydrochlorothiazide. In conclusion, telmisartan and nifedipine are both effective in improving insulin signalling in human hypertension; however, telmisartan seems to have broader effects. The combination treatment lercanidipine + enalapril seems to be more effective than lercanidipine + hydrochlorothiazide in activating insulin signalling in human lympho-monocytes.

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.

Effects of losartan and enalapril at different doses on cardiac and renal interstitial matrix in spontaneously hypertensive rats.

We have evaluated the effects of an ACE inhibitor, enalapril (ENA) and of an angiotensin II receptor blocker, losartan (LOS), administered either at hypotensive or non-hypotensive dosage, on the cardiac and renal structure of spontaneously hypertensive rats (SHR). Forty-eight rats were included in the study: eight SHR were treated with low-dose (ld, 1 mg/kg/day) ENA; eight with low-dose (ld, 0.5 mg/kg/day) LOS; eight with high-dose (hd, 25 mg/kg/day) ENA; eight with high-dose (hd, 15 mg/kg/day) LOS; while eight Wistar-Kyoto (WKY) and eight SHR were kept untreated (unt). Treatment was given from the 4th to the 12th week of age. Systolic blood pressure (SBP) was measured non-invasively every week. The left ventricular weight to body weight (RLVM) and the left + right kidney weight (RKW) to body weight was measured, and the cardiac and glomerular interstitial collagen content was evaluated using sirius red staining and image analysis. In addition, cardiac metalloproteinases activity (43 kDa MMP, MMP-2, and MMP-9) was evaluated by zymography. A significant reduction in RLVM was observed in SHR given ENA hd or LOS hd. Cardiac collagen was significantly reduced in SHR ENA hd and SHR LOS hd as well as in SHR LOS ld, but not in SHR ENA ld. The 43 kDa MMP collagenase activity was greater in WKY unt compared with SHR unt, being normalized only in SHR ENA hd. The gelatinase activity of MMP-9 showed a trend similar to 43 kDa MMP, but differences between SHR and WKY unt were only of borderline statistical significance. No difference among groups was observed in MMP-2 activity. No significant differences in RKW was observed between groups. However, the collagen content in the glomerular perivascular space was significantly reduced in all treated groups, including those given ld, compared with SHR unt. In conclusion, LOS and ENA showed a similar preventive effect on the increase of RLVM in SHR, but, at least in part, different effects on the extracellular matrix in different organs, being cardiac collagen less sensitive to low dose (ld) ACE inhibition.