Anti-hypertensive vasodilatory action of Gynura procumbens mediated by kaempferol 3-O-rutinoside

Introduction: Gynura procumbens (GP), otherwise known as longevity spinach or “Sambung Nyawa” in Malay, is an evergreen herb found in Africa and Southeast Asian countries (including Brunei) used traditionally to treat various diseases such as fever, diabetes and hypertension. We examined GP’s vasodilatory action to determine its possible role via the cholinergic-mediated pathway. Methods: GP leaves were prepared by filtration and evaporation to obtain the aqueous (AEGP) and methanol (MEGP) extracts followed by screening for phytochemical constituents. The total phenol, total flavonoid and flavonol contents were determined using the corresponding Folin–Ciocalteau, and aluminium colorimetric methods and the presence of kaempferol 3-O-rutinoside in the extracts was detected using HPLC analysis. Organ bath studies were conducted to determine the vasodilatory activity using intact and denuded isolated rat aortic rings by exposure to either increasing concentration of extracts (0.25, 0.5, 1.0, and 2.0 mg/mL) or 10 µg/mL kaempferol 3-O-rutinoside in the presence or absence of acetylcholine (ACh) after pre-contraction by noradrenaline (NA). Results: MEGP contained more phytochemical constituents and higher content of total flavonoid and total flavonol but less phenolic content than AEGP. Furthermore, MEGP yielded a 20% elevated amount of kaempferol 3-O-rutinoside than AEGP. Both extracts significantly amplified ACh-endothelium dependent vasodilation and mediated relaxation at 1 mg/mL in endothelium-intact and endothelium-denuded aortic rings with MEGP as a more effective vasodilator than AEGP. Overall, these results imply the involvement of extracts in potentiating cholinergic pathway, which might be mediated by kaempferol, as shown by its vasorelaxation effects in endothelium-intact and –denuded aorta. Conclusions: The present findings demonstrate that the vasodilatory activities of the two Gynura procumbens extracts, AEGP and MEGP, in thoracic aorta rings isolated from rats are potentially mediated via a cholinergic pathway through the action of a flavonoid particularly kaempferol 3-O-rutinoside.

Participation of NO in the vasodilatory action of isoespintanol

Background: accumulating evidence suggests that natural compounds and specifically monoterpenes exert a vasodilator action. Objetive: to investigate the vascular effects of isoespintanol (2-isopropil-3,6- dimetoxi-5-metilfenol, ISO) monoterpene isolated from the leaves of Oxandra cf xylopioides. Methods: thoracic aortic rings isolated from Wistar rats were contracted with KCl 80 mM and then relaxed by exposure to Ca2+-free solution in absence and in presence of ISO 0.6 mg/mL. The force/tissue ratio (F/W) and the time to obtain 50% of relaxation (T-50) were used to assess the maximal contractile response and the relaxation, respectively. To examine the participation of NO additional experiments were performed under inhibition of nitric oxide synthase with L-NAME (L-NG-Nitroarginine methyl ester). Results: ISO significantly decreased the F/W ratio (257 ± 19 vs. 360 ± 18) and did not change T-50. In presence of L-NAME the effects of ISO on contractile response was abolished. Conclusions: these results demonstrate that ISO exerts a vasodilator effect through NO- dependent pathways and suggest that an inhibition of calcium influx could be the involved mechanism.

Pycnogenol supplementation as an adjunct treatment for antidepressant-induced sexual dysfunction

Introduction Major depressive disorder is a serious mental disorder in which treatment with antidepressant medication is associated with incidence of adverse events, such as constipation, diarrhea, dry mouth, headache, insomnia, and sexual dysfunction (SDys). Escitalopram (ESC), an effective and safe selective serotonin reuptake inhibitor with good tolerability, was used in this study. In this study, we investigated the prospective effect of Pycnogenol (PYC), an antioxidant, anti-inflammatory, and vasodilator agent, on ESC-induced SDys. Methods This was a randomized, parallel, open-label study. Seventy-two outpatients of both genders with depression were randomized into two groups as follows: 37 patients from the ESC + PYC group took 50 mg of PYC per day for 4 months in ESC co-treatment, and 35 subjects from the ESC group took ESC only. Five patients dropped out and were excluded from the analysis. The participants were examined every month (visits 1–4). Results ESC use led to improvement of depressive symptoms and severity scored by standardized psychiatric tests. PYC co-treatment resulted in attenuation of SDys beginning at 1 month of treatment and continuing for two consecutive months. Furthermore, an increase in heart rate in the PYC group was registered. Conclusions We propose that PYC-mediated SDys attenuation is based on its ability to improve endothelial functions by its antioxidant, anti-inflammatory, vasodilatory, and anticoagulant action. We assume that the action of PYC on heart rate is in accordance with the aforementioned vasodilatory action of PYC and consequent baroreflex-mediated heart rate response. PYC co-treatment reduced ESC-induced SDys and elevated heart rate.

NSAIDs and heart failure: A dangerous relationship

One of the potential cardiotoxic action of anti-inflammatory drugs is the occurrence of heart failure (HF), due to their effects on fluid retention and blood pressure. The risk of hospitalization for HF is roughly doubled for both Coxibs, cyclooxygenase-1 (COX-1) and cyclooxygenase- 2 (COX-2) inhibitors, and all the conventional nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs are also associated with a risk of vascular thrombosis, which for NSAIDs is different in relation to their different ability to inhibit COX-1 and COX-2. The cardiovascular toxicity of these drugs in the direction of HF follow different pathways respect to their related vascular thrombosis toxicity and involves, in particular, the renal prostaglandins, PGE2 and prostacyclin, mostly synthesized by COX-2. In the kidneys the PGs perform a direct vasodilatory action, e.g. by means of non-contrasting angiotensin mechanisms, and for this reason nimesulide effects on renal microcirculation are independent from the prevalence of intrarenal renin angiotensin aldosterone system (RAAS) activity. Conversely, nimesulide reduces sodium tubular urinary flow only in presence of intrarenal RAAS.

The use of desflurane for neurosurgical procedures in rhesus macaque (Macaca mulatta)

Volatile agents are widely used to anaesthetise laboratory non-human primates as they allow a rapid induction and recovery as well as an easy adjustment of the anaesthesia plan. Desflurane is currently the volatile agent with the lowest solubility in blood, and hence enables the most rapid onset of anaesthesia and most rapid recovery. This study aimed to investigate the suitability of desflurane for maintenance of general anaesthesia in rhesus macaques undergoing elective experimental neurosurgery. Fourteen primates (five males and nine females) were sedated with ketamine (10 mg kg−1) and anaesthesia was induced with propofol (usually 8 mg kg−1 IV). Anaesthesia was maintained with desflurane (5.9 ± 0.8 %) and alfentanil (0.2–0.5 µg kg−1 min−1 IV). Animals were mechanically ventilated. Meloxicam (0.3 mg kg−1) and methylprednisolone infusion (5.4 mg kg−1 h−1) were also administered. All the primates were successfully anaesthetised and no severe complications related to the procedure or the anaesthesia regimen occurred. No major differences in physiological parameters and recovery times between the male and female groups were found. Emergence from anaesthesia was rapid (male 5.2 ± 2.4 min; female 4.1 ± 1.7 min) but its quality was assessed as equivalent to two other volatile anaesthetics, isoflurane and sevoflurane. These had previously been assessed for neuroanaesthesia in rhesus macaques. In conclusion, this study demonstrated that desflurane was suitable for maintenance of general anaesthesia for elective experimental neurosurgical procedures in rhesus macaque. However the vasodilatory action of the desflurane may limit its use in cases of severe intracranial hypertension or systemic hypotension.

Nitroxyl donors retain their depressor effects in hypertension

Nitroxyl (HNO), the redox congener of nitric oxide, has numerous vasoprotective actions including an ability to induce vasodilation and inhibit platelet aggregation. Given HNO is resistant to scavenging by superoxide and does not develop tolerance, we hypothesised that HNO would retain its in vivo vasodilatory action in the setting of hypertension. The in vitro and in vivo vasodilator properties of the HNO donors Angeli's salt (AS) and isopropylamine/NONOate (IPA/NO) were compared with the NO˙ donor diethylamine/NONOate (DEA/NO) in spontaneously hypertensive rats (SHR) and normotensive [Wistar-Kyoto (WKY) rats]. AS (10, 50, and 200 μg/kg), IPA/NO (10, 50, and 200 μg/kg), and DEA/NO (1, 5, and 20 μg/kg) caused dose-dependent depressor responses in conscious WKY rats of similar magnitude. Depressor responses to AS and IPA/NO were significantly attenuated ( P < 0.01) after infusion of the HNO scavenger N-acetyl-l-cysteine (NAC), confirming that AS and IPA/NO function as HNO donors in vivo. In contrast, responses to DEA/NO were unchanged following NAC infusion. Depressor responses to AS and IPA/NO in conscious SHR retained their sensitivity to the inhibitory effects of NAC ( P < 0.01), yet those to DEA/NO in SHR were significantly ( P < 0.05) enhanced following NAC infusion. Importantly, depressor responses to AS, IPA/NO, and DEA/NO were preserved in hypertension and vasorelaxation to AS and DEA/NO, in isolated aorta, unchanged in SHR as compared with WKY rats. This study has shown for the first time that HNO donors exert antihypertensive effects in vivo and may, therefore, offer a therapeutic alternative to traditional nitrovasodilators in the treatment of cardiovascular disorders such as hypertension.