Anticonstriction Effect of MCA in Rats by Danggui Buxue Decoction

Objective: Danggui Buxue decoction (DBD), consisting of Angelicae Sinensis Radix (ASR) and Astragali Radix (AR), is a famous prescription with the function of antivasoconstriction. This study intends to probe its mechanisms on the relaxation of the middle cerebral artery (MCA).Methods: Vascular tension of rat MCA was measured using a DMT620 M system. First, the identical series of concentrations of DBD, ASR, and AR were added into resting KCl and U46619 preconstricted MCA. According to the compatibility ratio, their dilatation effects were further investigated on KCl and U46619 preconstricted vessels. Third, four K+ channel blockers were employed to probe the vasodilator mechanism on KCl-contracted MCA. We finally examined the effects of DBD, ASR, and AR on the vascular tone of U46619-contracted MCA in the presence or absence of Ca2+.Results: Data suggested that DBD, ASR, and AR can relax on KCl and U46619 precontracted MCA with no effects on resting vessels. The vasodilator effect of ASR was greater than those of DBD and AR on KCl-contracted MCA. For U46619-contracted MCA, ASR showed a stronger vasodilator effect than DBD and AR at low concentrations, but DBD was stronger than ASR at high concentrations. Amazingly, the vasodilator effect of DBD was stronger than that of AR at all concentrations on two vasoconstrictors which evoked MCA. The vasodilator effect of ASR was superior to that of DBD at a compatibility ratio on KCl-contracted MCA at low concentrations, while being inferior to DBD at high concentrations. However, DBD exceeded AR in vasodilating MCA at all concentrations. For U46619-constricted MCA, DBD, ASR, and AR had almost identical vasodilation. The dilation of DBD and AR on KCl-contracted MCA was independent of K+ channel blockers. However, ASR may inhibit the K+ channel opening partially through synergistic interactions with Gli and BaCl2. DBD, ASR, and AR may be responsible for inhibiting [Ca2+]out, while ASR and AR can also inhibit [Ca2+]in.Conclusion: DBD can relax MCA with no effects on resting vessels. The mechanism may be related to ASR’s inhibition of KATP and Kir channels. Meanwhile, the inhibition of [Ca2+]out by DBD, ASR, and AR as well as the inhibition of [Ca2+]in by ASR and AR may contribute to dilate MCA.

Cardiac Depressant and Vasodialatory Effect of Flaxseed - Basis for the Medicinal use in Hypertension

Linum usitatissimum (Flaxseed) is known to be traditionally used for managing hypertension. In this study, we aim to provide a mechanistic basis for the medicinal use of Flaxseed in hypertension. The high-performance liquid chromatography (HPLC) analysis that we carried out during our study showed the presence of polar compounds (quercetin, nicotinic acid, and nicotinamide) in Flaxseed’s crude extract (Fs.Cr; aqueous methanolic). In anesthetized rats, Fs.Cr reduced arterial blood pressure (BP) dose-dependently (10-100 mg/kg). When tested for its mechanism of action ex vivo, Fs.Cr inhibited both the force and rate of spontaneous contractions in the dose range of 1-10 mg/mL in isolated guinea-pig atria, similar to how verapamil, a standard Ca+2 channel blocker does it. Further, Fs.Cr showed vasodilator effect against the contractions induced by phenylephrine (PE, 1 μM) in rat aortic ring preparations (concentration range: 1-10 mg/mL), whereas no effect was observed against the contractions induced by low K+ (25 mM) as well as high K+ (80 mM). This selective inhibitory effect of Fs.Cr against PE was tested for endothelium-dependent nitric oxide (NO) and/or cholinergic component involvement. The vasodilator effect of Fs.Cr against PE was retested in the absence and presence of atropine in endothelium (E)-intact and E-denuded aorta, but no significant shift was observed in the inhibitory effect of Fs.Cr. Further, Fs.Cr shifted the PE-induced concentration-response curves (CRCs) to the right in a dose-dependent manner (1 and 3 mg/mL). This effect was similar to that of prazosin. All these findings indicate that Flaxseed may mediate its antihypertensive activity by the alpha-1 receptor antagonist and Ca+2 channel blocking-like activity, which may account for its efficacy in hypertension.

Chemical composition and vasodilator activity of different Alpinia zerumbet leave extracts, a potential source of bioactive flavonoids

A polyphenol-rich extract with an expressive vasodilator effect was obtained from fresh leaves of Alpinia zerumbet (AZ), a medicinal plant. The vasodilator effects of AZ obtained from different extraction conditions were studied in perfused mesenteric vascular bed, and total polyphenol content (TPC) was determined for all samples. Chemical composition of AZ was analyzed by UHPLC/ESI-QTOF-MS, and a list of putative compounds was obtained by a molecular network. Briefly, results obtained indicate a 50% hydroethanolic extract from fresh leaves (AZE4) as the best extraction condition, presenting the greatest vasodilator effect (ED 50 = 7.1 µg ± 1.73) and TPC (16.30 mg GAE/g ± 0.44). Flavonoids were detected as main constituents and alpinetin, kaempferol-3-O-glucuronide, (-)- epicatechin and pinocembrin were identified as major compounds. The last effective extraction condition was 50% hydroethanolic extract from dried leaves without heating, which showed the smallest vasodilator response (ED 50 = 29.1 µg ± 4.3) and TPC (6.35 mg GAE/g ± 0.08), reinforcing the use of fresh leaves and heating step to improve extracts performance. The vasodilator effect and the main flavonoid composition of AZE4 provide experimental support for the indication of this extract as a potential source of bioactive flavonoids for the treatment of cardiovascular diseases.

Relationship between endothelin and nitric oxide pathways in the onset and maintenance of hypertension in children and adolescents

The mechanisms that regulate blood pressure are numerous and complex; one mechanism that plays an important role in this scenario is represented by the balance between the vasoconstrictor effect of endothelin-1 and the vasodilator effect of nitric oxide. While there is agreement on the fact that increased endothelin-1 activity and decreased nitric oxide bioavailability are present in hypertensive adults, the situation is less clear in children and adolescents. Not all studies agree on the finding of an increase in plasma endothelin-1 levels in hypertensive children and adolescents; in addition, the picture is often confused by the concomitant presence of obesity, a condition that stimulates the production of endothelin-1. Furthermore, there is recent evidence that, in younger obese and hypertensive subjects, there is an overproduction of nitric oxide, rather than a reduction. This condition may change over time, causing endothelial dysfunction due to a reduced availability of nitric oxide in hypertensive adolescents. The purpose of this review is to address the main biochemical and pathophysiological aspects of endothelin and nitric oxide involvement in hypertension and to summarize the available scientific evidence on their role in the onset and maintenance of high blood pressure in children and adolescents.

Identification of Compounds With Vasoactive Properties in a Pitaya Juice Extract (Stenocereus griseus)

Objectives The objective of this study is to identify the vasoactive compounds present in the pitaya juice extract (PJE) and evaluate its effect using in vivo and in vitro models. Methods First, the pitaya juice was obtained from the fruit of Stenocereus Griseus, centrifuged to obtain PJE. Six hundred mL of PJE was frozen until its use and other 600 mL was lyophilized and stored. The lyophilized PJE was analyzed by HPLC-PAD. The wavelengths for detection in the PAD system were 535 and 480 nm for betalains, and 370 and 280 nm for phenolic compounds. On the other hand, the vasoactive effect of PJE was evaluated in isolated rings of thoracic aortas, with (n = 5) and without endothelium (n = 5), of male Wistar rats (250–350 g) previously contracted with phenylephrine (10 mM to 10 μmol/L), followed by the administration of a concentration of 20 mg/mL of lyophilized PJE and 1 mL physiological solution, as a control (30 min of treatment). Results The profiling of lyophilized PJE by HPLC-PAD showed 16 types of betalains and 31 types of phenolic compounds, which will be analyzed by mass spectrometry. Isolated aortic rings (in presence and absence of the endothelium) administered with PJE showed 8-fold greater vasodilation compared to the control (54.3% ± 14.1 vs 6.7% ± 3.7), suggesting that the compounds present in the PJE may exert a vasodilator effect, of which its action mechanism will be investigated. Conclusions Pitaya juice extract contains vasoactive compounds such as betalains and phenolic compounds, which could be responsible for PJE exerting a vasodilator effect that was observed in assays of isolated rat aortic rings. Funding Sources 1. Consejo Nacional de Ciencia y Tecnología (CONACYT) 2. Instituto Potosino de Investigación Científica y Tecnológica A.C. (IPICYT).

VASODILATOR EFFECT OF OCTYLMETHOXYCINNAMATE ON HUMAN UMBILICAL ARTERIES

Octylmethoxycinnamate (OMC) is a filter for ultraviolet B radiation used in sunscreens to protect skin. There is some evidence about the OMC activity as endocrine disruptor concerning a possible estrogenic activity, but its vascular effects were not still analyzed. The objective was to evaluate the non-genomic effects of the OMC on human umbilical artery (HUA) without endothelium. By mean of an organ bath system, HUA rings without endothelium were contracted by 5-hydroxytryptamine (5HT; 1µM) or by depolarization with KCl (60mM), and the effect of different concentrations of OMC was analyzed. The OMC elicits vasodilator effect on HUA without endothelium contracted by 5-HT (1μM) and by KCl (60mM). The effect was similar for the two contractile agents used. Here, we established that the OMC causes vasodilation of human arteries. This effect is analogous to the non-genomic effect caused by estradiol (E2), which occurs also by and endothelial-independent mechanism.