Vasodilatory Effects Research Articles

Case Report: Sympathetic crashing acute pulmonary edema – only “NIV and nitroglycerin”?

Introduction An 84-year-old male patient alerted EMS because of severe dyspnea and subsequently presented with respiratory failure due to sympathetic crashing acute pulmonary edema (SCAPE.) The term SCAPE was coined outside Europe, with guidance on treatment only reflecting drugs available in the US and omitting potentially effective options, as highlighted in this report.[1] Diagnostic findings The patient presented sweating, pale and tachypneic with auscultatory crackles, radial pulse was palpable. He was able to follow commands, but unable to communicate verbally due to dyspnea. Initial SpO2 showed 80%, NIBP 185/105mmHg. The patient described sudden onset dyspnea as the only symptom. An ECG showed sinus tachycardia and LBBB (SGARBOSSA negative.) ABG showed hypoxemia and acidosis due to hypercapnia and lactatemia. Main diagnosis In absence of other causes for flash pulmonary edema, SCAPE was suspected. Therapeutic interventions The patient was supported in sitting position, oxygen applied, a total of 25mg urapidil and 7mg morphine administered intravenously, non-invasive ventilation (CPAP+ASB, PEEP 5mbar, ΔASB 5mbar) initiated and an arterial line placed for invasive blood pressure measurement and ABG. Outcome While RSI was considered multiple times, the patient improved rapidly during transport and a short NIV duration at the emergency department and was transferred to the ward without further interventions. Discussion With reducing afterload as main goal of pharmacological therapy, urapidil could be as effective as high-dose i.v. nitroglycerine, which is currently recommended.[2,3] While lacking the effect of venous vasodilation and thus not reducing preload, its effect on sympathetic tone via 5-HT1A-receptors supplemental to affecting arterial vasodilation via α-receptors might make it equally effective while being easier to administer. No data is available comparing urapidil to high-dose nitroglycerin, while it has proven more effective than low-dose nitroglycerin.[4]

Cardiovascular Effects of Stimulators of Soluble Guanylate Cyclase Administration: A Meta-analysis of Randomized Controlled Trials.

Heart failure (HF) is one of the main causes of cardiovascular mortality in the western world. Despite great advances in treatment, recurrence and mortality rates remain high. Soluble guanylate cyclase is an enzyme which, by producing cGMP, is responsible for the effects of vasodilation, reduction of cardiac pre- and after-load and, therefore, the improvement of myocardial performance. Thus, a new therapeutic strategy is represented by the stimulators of soluble guanylate cyclase (sGCs). The aim of this meta-analysis was to analyze the effects deriving from the administration of sGCs, in subjects affected by HF. A systematic literature search of Medline, SCOPUS, and Google Scholar was conducted up to December 2022 to identify RCTs assessing the cardiovascular effects, as NT-pro-BNP values and ejection fraction (EF), and all-cause mortality, of the sGCs. Quantitative data synthesis was performed using a random-effects model, with weighted mean difference (WMD) and 95% confidence interval (CI) as summary statistics. The results obtained documented a statistically significant improvement in NT-proBNP values (SMD: - 0.258; 95% CI: - 0.398, - 0.118; p < 0.001) and EF (WMD: 0.948; 95% CI: 0.485, 1.411; p < 0.001) in subjects treated with sGCs; however, no significant change was found in the all-cause mortality rate (RR 0.96; 95% CI 0.868 to 1.072; I2, p = 0). The sGCs represent a valid therapeutic option in subjects suffering from HF, leading to an improvement in cardiac performance.

Evaluation of Hypotensive and Vasodilatory Effects of Murraya koenigii Leaves Extract in L-NAME Induced Hypertensive Rats in Relation with Muscarinic Receptors

Evaluation of Hypotensive and Vasodilatory Effects of Murraya koenigii Leaves Extract in L-NAME Induced Hypertensive Rats in Relation with Muscarinic Receptors

Dilation of Pregnant Rat Uterine Arteries with Phenols from Extra Virgin Olive Oil Is Endothelium-Dependent and Involves Calcium and Potassium Channels.

During pregnancy, uterine vasculature undergoes significant circumferential growth to increase uterine blood flow, vital for the growing feto-placental unit. However, this process is often compromised in conditions like maternal high blood pressure, particularly in preeclampsia (PE), leading to fetal growth impairment. Currently, there is no cure for PE, partly due to the adverse effects of anti-hypertensive drugs on maternal and fetal health. This study aimed to investigate the vasodilator effect of extra virgin olive oil (EVOO) phenols on the reproductive vasculature, potentially benefiting both mother and fetus. Isolated uterine arteries (UAs) from pregnant rats were tested with EVOO phenols in a pressurized myograph. To elucidate the underlying mechanisms, additional experiments were conducted with specific inhibitors: L-NAME/L-NNA (10-4 M) for nitric oxide synthases, ODQ (10-5 M) for guanylate cyclase, Verapamil (10-5 M) for the L-type calcium channel, Ryanodine (10-5 M) + 2-APB (3 × 10-5 M) for ryanodine and the inositol triphosphate receptors, respectively, and Paxilline (10-5 M) for the large-conductance calcium-activated potassium channel. The results indicated that EVOO-phenols activate Ca2+ signaling pathways, generating nitric oxide, inducing vasodilation via cGMP and BKCa2+ signals in smooth muscle cells. This study suggests the potential use of EVOO phenols to prevent utero-placental blood flow restriction, offering a promising avenue for managing PE.

Endoplasmic Reticulum Stress Induces Vasodilation in Liver Vessels That Is Not Mediated by Unfolded Protein Response.

There is a growing body of evidence that ER stress and the unfolded protein response (UPR) play a key role in numerous diseases. Impaired liver perfusion and ER stress often accompany each other in liver diseases. However, the exact impact of ER stress and UPR on the hepatic perfusion is not fully understood. The aim of this study was to disclose the effect of ER stress and UPR on the size of liver vessels and on the levels of Ca2+ and nitric oxide (NO), critical regulators of vascular tonus. This study was carried out in precisely cut liver tissue slices. Confocal microscopy was used to create 3D images of vessels. NO levels were determined either using either laser scan microscopy (LSM) in cells or by NO-analyser in medium. Ca2+ levels were analysed by LSM. We show that tunicamycin, an inducer of ER stress, acts similarly with vasodilator acetylcholine. Both exert a similar effect on the NO and Ca2+ levels; both induce significant vasodilation. Notably, this vasodilative effect persisted despite individual inhibition of UPR pathways-ATF-6, PERK, and IRE1-despite confirming the activation of UPR. Experiments with HUVEC cells showed that elevated NO levels did not result from endothelial NO synthase (eNOS) activation. Our study suggests that tunicamycin-mediated ER stress induces liver vessel vasodilation in an NO-dependent manner, which is mediated by intracellular nitrodilator-activatable NO store (NANOS) in smooth muscle cells rather than by eNOS.

Preferential vasodilator effects of levosimendan in resistance pulmonary arteries in a rodent pulmonary embolism model

Background: We compared the vasoactive effects of levosimendan on isolated conduit pulmonary arteries (CPA) and resistance pulmonary arteries (RPA) versus mesenteric arteries, and we assessed the pulmonary artery (PA) vascular function and the PA vasoactive effects of levosimendan in a rodent pulmonary embolism (PE) model.Methods: One group of male Wistar rats (200-300 g) was killed by decapitation to obtain pulmonary and mesenteric rings. Another group was assigned to a massive PE or saline solution infusion. After euthanasia, mesenteric arteries and CPA (1-2 mm) and RPA (≤0.5 mm) were dissected and cut into 2-3 mm wide rings, recording contractile tension. We obtained the concentration-response curves of cumulative doses of levosimendan on pre-contracted arterial rings from decapitated and sham/embolized animals. A set of RPA rings was exposed to acute hypoxia. The effect of PE on the pulmonary vasoactive function was assessed by dose-response curves of acetylcholine (ACh) and endothelin-1 (ET-1) of PA rings from sham/embolized animals.Results: Levosimendan relaxant potency of RPA was similar to that of mesenteric arteries and higher than CPA, while mesenteric rings showed the maximal relaxant effect, followed by RPA and CPA, respectively. PE did not affect the vasoactive response of PA rings either to ACh or to ET-1, and the relaxant effects of CPA and RPA to levosimendan were also preserved. Acute hypoxia reduced (p&lt;0.05) but did not avoid the RPA relaxant effect of levosimendan.Conclusions: Levosimendan is a more specific vasodilator of RPA with a similar relaxant potency as mesenteric arteries, which is preserved after PE but significantly reduced during hypoxia.

Non-invasive perfusion MR imaging of the human brain via breath-holding

Dynamic susceptibility contrast (DSC) MRI plays a pivotal role in the accurate diagnosis and prognosis of several neurovascular diseases, but is limited by its reliance on gadolinium, an intravascularly injected chelated metal. Here, we determined the feasibility of measuring perfusion using a DSC analysis of breath-hold-induced gradient-echo-MRI signal changes. We acquired data at both 3 T and 7 T from ten healthy participants who engaged in eight consecutive breath-holds. By pairing a novel arterial input function strategy with a standard DSC MRI analysis, we measured the cerebral blood volume, flow, and transit delay, and found values to agree with those documented in the literature using gadolinium. We also observed voxel-wise agreement between breath-hold and arterial spin labeling measures of cerebral blood flow. Breath-holding resulted in significantly higher contrast-to-noise (6.2 at 3 T vs. 8.5 at 7 T) and gray matter-to-white matter contrast at higher field strength. Finally, using a simulation framework to assess the effect of dynamic vasodilation on perfusion estimation, we found global perfusion underestimation of 20–40%. For the first time, we have assessed the feasibility of and limitations associated with using breath-holds for perfusion estimation with DSC. We hope that the methods and results presented in this study will help pave the way toward contrast-free perfusion imaging, in both basic and clinical research.

Open Lumbar Sympathectomy on Buerger’s Disease: A Case Report

Thromboangiitis obliterans known as Buerger's disease is a nonatherosclerotic, progressive inflammatory disease that affects small and medium arteries in the upper and lower extremities. Strong relationship was found between the development of this disease and the patient's history of smoking. We reported a case of 50-year-old male with progressive pain in fingers of right leg with darkened ulcer. Open lumbar sympathectomy is a procedure that is rarely performed nowadays, but progressive pain in buerger’s disease patients can be managed with this procedure. The aim of sympathectomy is to reduce sympathetic response causing vasodilation effect which will reduce rest pain.

THE ADVANTAGES OF SYDNONIMINES COMPARED TO NITRATES IN THE TREATMENT OF PATIENTS WITH ISCHEMIC HEART DISEASE AND CORONARY INSUFFICIENCY

One of the primary challenges in treating patients with coronary artery disease and coronary insufficiency using nitrates is the development of tolerance. Nitrate tolerance is a condition in which the duration and intensity of anti-anginal and anti-ischemic effects decrease, despite maintaining a high concentration of the drug in the blood. In cases of developing tolerance, a continual increase in the nitrate dose is necessary to achieve the previous effect. To eliminate developed nitrate tolerance, discontinuing nitrates for 3-5 days is typically sufficient. Currently, molsidomine is employed as an alternative to nitrates, with sydnonimines emerging as a noteworthy substitute. Among sydnonimines, molsidomine (marketed as Sydnopharm, Dilasidom, Corvaton) stands out as the most effective. Despite its chemical distinction from nitrates, molsidomine operates through a similar mechanism. Functioning as a nitric oxide donor, this antianginal drug avoids the development of tolerance even with prolonged use. Molsidomine, akin to nitrates, acts as a vasodilator, exhibiting efficacy as an anti-ischemic and anti-anginal medication when administered in appropriate doses. Upon entering the human body, molsidomine undergoes hepatic metabolism, transforming into an active derivative compound known as SIN-1. This metabolite, upon entering the bloodstream, further converts into an active form (SIN-1A). From this active metabolite, the nitric oxide (NO) group is released, influencing the activation of guanylate cyclase. This activation prompts guanosine triphosphate to convert into cyclic guanosine triphosphate, ultimately contributing to the synthesis of proteins that bind calcium. This cascade of events results in the vasodilatory effect of molsidomine. Indications for molsidomine include stable angina pectoris, acute coronary syndrome, early post-infarction angina, congestive heart failure, portal hypertension, pulmonary hypertension, and Aerz's disease. Possible side effects following the therapy with molsidomine (dizziness, headache, and diplopia) occur much less frequently compared to nitrates. After using nitrates, such a side effect as methemoglobinемia may occur. Therapy with molsidomine does not lead to the development of this side effect.

Regulatory role of peroxynitrite in advanced glycation end products mediated diabetic cardiovascular complications.

The Advanced Glycation End Products (AGE) binding with its receptor can increase reactive oxygen species (ROS) generation through specific signaling mediators. The effect of superoxide (O2-) and O2- mediated ROS and reactive nitrogen species depends on their concentration and location of formation. Nitric oxide (NO) has anti-inflammatory and anticoagulant properties and a vasodilation effect, but NO can be deactivated by reacting with O2-. This reaction between NO and O2- produces the potent oxidant ONOO-. Therefore, ONOO-'s regulatory role in AGEs in diabetic cardiovascular complications must considered as a regulator of cardiovascular complications in diabetes.

Immediate angiographic control after intra-arterial nimodipine administration underestimates the vasodilatory effect

Intra-arterial nimodipine administration is a widely used rescue therapy for cerebral vasospasm. Although it is known that its effect sets in with delay, there is little evidence in current literature. Our aim was to prove that the maximal vasodilatory effect is underestimated in direct angiographic controls. We reviewed all cases of intra-arterial nimodipine treatment for subarachnoid hemorrhage-related cerebral vasospasm between January 2021 and December 2022. Inclusion criteria were availability of digital subtraction angiography runs before and after nimodipine administration and a delayed run for the most affected vessel at the end of the procedure to decide on further escalation of therapy. We evaluated nimodipine dose, timing of administration and vessel diameters. Delayed runs were performed in 32 cases (19 patients) with a mean delay of 37.6 (± 16.6) min after nimodipine administration and a mean total nimodipine dose of 4.7 (± 1.2) mg. Vessel dilation was more pronounced in delayed vs. immediate controls, with greater changes in spastic vessel segments (n = 31: 113.5 (± 78.5%) vs. 32.2% (± 27.9%), p < 0.0001) vs. non-spastic vessel segments (n = 32: 23.1% (± 13.5%) vs. 13.3% (± 10.7%), p < 0.0001). In conclusion intra-arterially administered nimodipine seems to exert a delayed vasodilatory effect, which should be considered before escalation of therapy.

Role of Hyperbaric Oxygen in Filler-Induced Vascular Occlusion.

The rising incidence of filler-induced vascular complications in the context of aesthetic procedures necessitates a thorough assessment of therapeutic options. Hyperbaric oxygen therapy (HBOT) has emerged as a potential intervention for filler-induced vascular occlusion (FIVO), although optimal dosing and timing remain undefined. This review explores the pathophysiology of FIVO and elucidates HBOT's multifaceted role in salvaging ischemic tissue. The physical and biochemical mechanisms of HBOT, including its vasodilatory, anti-spasmodic, and anti-inflammatory effects, are examined. HBOT serves as an adjunctive therapy in FIVO management, emphasizing timely intervention, adherence to specific pressures (two atmosphere absolute), and session durations (60 minutes) to optimize efficacy and minimize complications. While existing HBOT protocols for compromised grafts provide insights, standardized guidelines for FIVO are lacking. HBOT enhances tissue oxygenation, modulates reactive oxygen species, and influences angiogenesis and hypoxia response. However, it does not replace key treatment protocols for filler vascular complications. Further research and standardized protocols are warranted to define HBOT's definitive role in mitigating filler-induced vascular complications. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Oxidative Stress and Cerebral Vascular Tone: The Role of Reactive Oxygen and Nitrogen Species.

The brain's unique characteristics make it exceptionally susceptible to oxidative stress, which arises from an imbalance between reactive oxygen species (ROS) production, reactive nitrogen species (RNS) production, and antioxidant defense mechanisms. This review explores the factors contributing to the brain's vascular tone's vulnerability in the presence of oxidative damage, which can be of clinical interest in critically ill patients or those presenting acute brain injuries. The brain's high metabolic rate and inefficient electron transport chain in mitochondria lead to significant ROS generation. Moreover, non-replicating neuronal cells and low repair capacity increase susceptibility to oxidative insult. ROS can influence cerebral vascular tone and permeability, potentially impacting cerebral autoregulation. Different ROS species, including superoxide and hydrogen peroxide, exhibit vasodilatory or vasoconstrictive effects on cerebral blood vessels. RNS, particularly NO and peroxynitrite, also exert vasoactive effects. This review further investigates the neuroprotective effects of antioxidants, including superoxide dismutase (SOD), vitamin C, vitamin E, and the glutathione redox system. Various studies suggest that these antioxidants could be used as adjunct therapies to protect the cerebral vascular tone under conditions of high oxidative stress. Nevertheless, more extensive research is required to comprehensively grasp the relationship between oxidative stress and cerebrovascular tone, and explore the potential benefits of antioxidants as adjunctive therapies in critical illnesses and acute brain injuries.

The vasodilator effect of Eugenol on uterine artery – potential therapeutic applications in pregnancy-associated hypertension

Preeclampsia, a gestational associated hypertension, has been reported in 6–8% of pregnant women worldwide leading to premature delivery and low birth weight of newborn due to reduced blood flow to placenta. Although several vasodilators (Methyl dopa, hydralazine, β-blockers and diuretics) are currently in use to treat preeclampsia, still there is a search for safer drugs with better efficacy. Lately, antihypertensive vasodilators from natural sources are gaining importance in treating preeclampsia. Eugenol (Eug), a natural essential oil, has been traditionally used in health and food products without any risk. In the present study, ex vivo experiments were designed to examine the vasorelaxation effect of Eug and its signaling pathways in a middle uterine artery (MUA) of pregnant Capra hircus (Ch). In presence of different blockers (L-NAME, indomethacin, ODQ, Ouabain, glibenclamide, 4-AP, Ba2, Carbenoxolone and 18β Glycyrrhetinic acid), Eug-induced concentration-dependent vasorelaxation response was elicited. The results showed that Eug caused a greater vasorelaxation effect in the MU of pregnant animals, which is mediated by potential activation of eNOS, KATP channels, and Kir channels with moderate activation of Na+- K+- ATPase and sGC and MEGJ. These findings provide a strong basis for developing Eug as a therapeutic candidate in the treatment of pregnancy-associated hypertension.

Inhaled Nitric Oxide ReDuce postoperatIve pulmoNAry complicaTions in patiEnts with recent COVID-19 infection (INORDINATE): protocol for a randomised controlled trial

BackgroundA history of SARS-CoV-2 infection has been reported to be associated with an increased risk of postoperative pulmonary complications (PPCs). Even mild PPCs can elevate the rates of early postoperative...

CGRP attenuates pulmonary vascular remodeling by inhibiting the cGAS-STING-NFκB pathway in pulmonary arterial hypertension

BackgroundHyperproliferation, inflammation, and mitochondrial abnormalities in pulmonary artery smooth muscle cells (PASMCs) underlie the pathological mechanisms of vascular remodeling in pulmonary arterial hypertension (PAH). Cytoplasmic mtDNA activates the cGAS-STING-NFκB pathway and secretes pro-inflammatory cytokines that may be involved in the pathogenesis of PAH. Calcitonin gene-related peptide (CGRP) acts as a vasodilator to regulate patterns of cellular energy metabolism and has vasodilatory and anti-inflammatory effects. MethodsThe role of the cGAS-STING-NFκB signaling pathway in PAH vascular remodeling and the regulation of CGRP in the cGAS-STING-NFκB signaling pathway were investigated by echocardiography, morphology, histology, enzyme immunoassay, and fluorometry. ResultsMonocrotaline (MCT) could promote right heart hypertrophy, pulmonary artery intima thickening, and inflammatory cell infiltration in rats. Cinnamaldehyde (CA)-induced CGRP release alleviates MCT-induced vascular remodeling in PAH. CGRP reduces PDGF-BB-induced proliferation, and migration, and downregulates smooth muscle cell phenotypic proteins. In vivo and in vitro experiments confirm that the mitochondria of PASMCs were damaged during PAH, and the superoxide and mtDNA produced by injured mitochondria activate the cGAS-STING-NFκB pathway to promote PAH process, while CGRP could play an anti-PAH role by protecting the mitochondria and inhibiting the cGAS-STING-NFκB pathway through PKA. ConclusionThis study identifies that CGRP attenuates cGAS-STING-NFκB axis-mediated vascular remodeling in PAH through PKA.

Prospects for the creation of new phytochemical medicinal products based on Myrtus communis L. (a review)

The number of medicinal products based on biologically active substances (BAS) of plant origin is increasing every year. Scientists are exploring non-official plant raw materials used in non-traditional medicine to expand the raw material base for creating new phytopreparations. Among numerous plants, common myrtle (Myrtus communis L.), which is a fairly common indoor plant, is recognized as a valuable source of BAS. The aim of the work is to analyze and summarize new literature data on the botanical characteristics, chemical composition, pharmacological and toxicological properties of Myrtus communis L. Materials and methods. Data were collected from several legitimate databases and services such as PubMed, Medline, Scopus, Google Scholar, ResearchGate using the key terms “Myrtus communis L.”, “botanical characteristics”, “pharmacological studies”, “phytochemical studies” in each database data Relevant and related data were filtered as appropriate if deemed relevant to the topic of interest. Time frames have also been adjusted to provide up-to-date information. Results. Myrtus communis L., commonly known as common myrtle, is a widely recognized medicinal plant in the Mediterranean region. Various parts of this plant, including the leaves, fruits, and flowers, have been used in traditional medicine for treating a wide range of ailments. The pharmacological properties of common myrtle are attributed to the presence of essential oils and phenolic compounds, and these properties include antimicrobial, antiviral, antidiabetic, antispasmodic, vasodilator, antiulcer, antioxidant, antitumor, and anti-inflammatory effects. This article offers an overview of the botanical characteristics and chemical composition of different parts of common myrtle, and it presents a literature review of pharmacological studies that provide evidence for the plant’s medicinal properties. Conclusions. Common myrtle is a promising plant for further pharmacognostic research with the aim of expanding the raw material base, using the method of clonal micropropagation and creating new phytopreparations based on it.

The Role of Catestatin in Preeclampsia.

Preeclampsia (PE) is a unique pregnancy disorder affecting women across the world. It is characterized by the new onset of hypertension with coexisting end-organ damage. Although the disease has been known for centuries, its exact pathophysiology and, most importantly, its prevention remain elusive. The basis of its associated molecular changes has been attributed to the placenta and the hormones regulating its function. One such hormone is chromogranin A (CgA). In the placenta, CgA is cleaved to form a variety of biologically active peptides, including catestatin (CST), known inter alia for its vasodilatory effects. Recent studies indicate that the CST protein level is diminished both in patients with hypertension and those with PE. Therefore, the aim of the present paper is to review the most recent and most relevant in vitro, in vivo, and clinical studies to provide an overview of the proposed impact of CST on the molecular processes of PE and to consider the possibilities for future experiments in this area.

Vasodilation and Blood Pressure-Lowering Effect of 3-Demethyl-2-Geranyl-4-Prenylbellidifoline, a Xanthone Obtained from Garcinia achachairu, in Hypertensive Rats.

3-demethyl-2-geranyl-4-prenylbellidifoline (DGP), a natural xanthone isolated from Garcinia achachairu, has previously demonstrated remarkable diuretic and renal protective actions. The present study expands its actions on the cardiovascular system by evaluating its vasorelaxant and blood pressure-lowering effects in spontaneously hypertensive rats (SHRs). Aortic endothelium-intact (E+) preparations of SHRs pre-contracted by phenylephrine and exposed to cumulative concentrations of G. achachairu extract, fractions, and DGP exhibited a significant relaxation compared to vehicle-only exposed rings. The non-selective muscarinic receptor antagonist (atropine), the non-selective inhibitor of nitric oxide synthase (L-NAME), as well as the inhibitor of soluble guanylate cyclase (ODQ) altogether avoided DGP-induced relaxation. Tetraethylammonium (small conductance Ca2+-activated K+ channel blocker), 4-aminopyridine (a voltage-dependent K+ channel blocker), and barium chloride (an influx-rectifying K+ channel blocker) significantly reduced DGP capacity to induce relaxation without the interference of glibenclamide (an ATP-sensitive inward rectifier 6.1 and 6.2 K+ channel blocker). Additionally, administration of DGP, 1 mg/kg i.v., decreased the mean, systolic, and diastolic arterial pressures, and the heart rate of SHRs. The natural xanthone DGP showed promising potential as an endothelium-dependent vasorelaxant, operating through the nitric oxide pathway and potassium channels, ultimately significantly reducing blood pressure in hypertensive rats.

Effects of vasodilators on beat-to-beat and every fifteen minutes blood pressure variability induced by noradrenaline infusion in rats

Increased blood pressure variability (BPV) was shown to be associated with cardiovascular morbidities and/or mortalities. There are various types of BPV depending on time intervals of BP measurements, ranging from beat-to-beat to visit-to-visit or year-to-year. We previously found that continuous infusion of noradrenaline (NA) for 14 days increased short-term BPV every 15 min in rats. The aims of this study were to examine (1) whether NA infusion increases very short-term beat-to-beat BPV, (2) the effects of azelnidipine and hydralazine on NA-induced BPV, and (3) whether baroreceptor reflex sensitivity (BRS) is affected by NA or NA plus those vasodilators. Nine-week-old Wistar rats infused subcutaneously with 30 μg/h NA were orally treated with or without 9.7 mg/day azelnidipine or 5.9 mg/day hydralazine over 14 days. BP levels were continuously monitored via abdominal aortic catheter with a telemetry system in an unrestrained condition. Standard deviations (SDs) were used to evaluate beat-to-beat BPV and BPV every 15 min which was obtained by averaging BP levels for 10-s segment at each time point. BRS was determined by a sequence analysis. Continuous NA infusion over 14 days increased average BP, beat-to-beat BPV, and BPV every 15 min, lowering BRS. Comparing the two vasodilators, hydralazine reduced BP elevation by NA; meanwhile, azelnidipine alleviated BPV augmentation, preserving BRS, despite a smaller BP reduction. Thus, NA infusion increased both very short- and short-term BPV concomitantly with impaired BRS, while azelnidipine had an inhibitory effect, possibly independent of BP-lowering, on those types of BPV and impairment of BRS.