Evaluation of a novel angiotensin II receptor 1 antagonist intesartan as anti-hypertension drug

Aim The preclinical studies of a novel angiotensin II receptor 1 antagonist 2-（4-（ （1,7＇-dimethyl-2＇- propyl-1H ,3 ＇H-2,5＇-bibenzo [ d ] imidazol-3＇-yl ） methyl） -1H-indol-l-yl ） benzoic acid （ intesartan ）. Methods The affinity to AT1 receptor of intesartan was tested through radioactive receptor binding assay by -y-counter. The anti-hypertensive activity in spontaneously hypertensive rats （SHRs） at different doses in vivo was tested by tail noninvasive arterial blood pressure measurement system. Pharmacokinetic parameters were analyzed by high per- formance liquid chromatography （HPLC） method. Besides, acute toxicity tests in ICR and Ames reverse mutation assay in tester strain （TA97, TA98, TA100 and TA102） was also detected. Results The binding assays sugges- ted that intesartan displayed high affinity to angiotensin II AT1 receptor with an ICs0 value of （0.36 ± 0. 18） nmol · L^-1. In vivo anti-hypertensive experiments showed that intesartan had an efficient and long-acting effect in reduc- ing blood pressure which could last more than 24 h at the doses of 2 mg· kg^-1, 5 mg · kg^-1 , and 10 mg · kg^-1 in spontaneously hypertensive rats. The minimum effective dose of it was 2 mg · kg^-1 and the T/P value was 54. 18%. Acute toxicity tests suggested that intesartan was safe with the LDs0 value of 526.20 mg · kg^-1. Ames assay proved that it would not cause the mutations of salmonella typhimurium. And the pharmacokinetic experiments showed that it could be absorbed efficiently and metabolized smoothly both in blood and in tissues in wistar rats. Conclusions Intesartan could be considered as a novel anti-hypertension candidate with efficient, long-acting and low toxicity chracteristics.

Effects of anti-hypertensive drugs on esophageal body contraction

AIM:To clarify the effects of anti-hypertensive drugs on esophageal contraction and determine their possi-ble relationship with gastro-esophageal reflux disease.METHODS:Thirteen healthy male volunteers were enrolled. Esophageal body peristaltic contractions and lower esophageal sphincter (LES) pressure were measured using high resolution manometry. All subjects were randomly examined on four separate occasions following administrations of nifedipine,losartan,and atenolol,as well as without any drug administration.RESULTS:Peristaltic contractions by the esophageal body were separated into three segments by two troughs. The peak peristaltic pressures in the mid and lower segments of the esophageal body under atenolol administration were signifi cantly higher than those without medication in a supine position. On the other hand,peristaltic pressures under nifedipine administration were lower than those observed without drug ad-ministration. Losartan did not change esophageal body peristalsis. Atenolol elevated LES pressure and slowed peristaltic wave transition,while the effects of nifedip-ine were the opposite. CONCLUSION:Among the anti-hypertensive drugs tested,atenolol enhanced esophageal motor activity,which was in contrast to nifedipine.

Anti-Hypertensive Effects of Blended <i>Camellia oleifera</i>Abel Oil and Eucommia Extract on SHR Mice

In our study, we employed Camellia seed oil as the main ingredients blended with Eucommia Extract to investigate the effects of anti-hypertensive on mice by administrating mice with low dose, middle dose and high dose of Camellia seed oil complex for 4 weeks. The specific tests of studying effects of anti-hypertensive were body weight, blood systolic pressure (BSP), diastolic blood pressure (DBP), pm meam blood pressure (MBP) and heart rate (HR). And the results showed that appropriate level of Camellia seed oil complex could decrease the body weight and had an active effect on the cardiovascular system of mice, which significantly embodied the anti-hypertensive activity of Camellia seed oil complex.

Exploring the Anti-Hypertensive Properties of Medicinal Plants and Their Bioactive Metabolites: An Extensive Review

Medicinal plants are extensively used in traditional folk medicine. High blood pressure is associated with the risk of cardiovascular diseases (CVDs) and many other serious health complications resulting from it as a major concern of morbidity and mortality in health sector. Use of diuretics, angiotensin converting enzyme (ACE) inhibitors, beta adrenergic receptor antagonists (beta blockers), alpha adrenergic receptor antagonists (alpha blockers), calcium channel blockers (CCBs) etc. are not efficient enough to cure hypertension. Side effects regarding these medications lead to intolerance, impaired control of the disease, and also mismanagement of therapy. So, approach regarding quenching new potent therapeutic compounds from medicinal plants draws attention nowadays. For example, as a first-line therapeutic agent, an alkaloid is highly effective in lowering systolic blood pressure which is isolated from root extract of the plant of Rauwolfia serpentina species, namely reserpine. This article comes up with a list of 63 plant species from 37 families, compiling information related to plant parts used for making extracts, types of extract and animals used in these studies, antihypertensive effect of the extracts etc. It also refers to 74 chemically defined molecules, with in vitro and in vivo anti-hypertensive potential, isolated from these extracts along with their dosage and mechanism of action by using electronic searches of published articles from various databases and reference books. Our present work would be beneficial for researchers to investigate and invent novel antihypertensive therapy to treat hypertension.

Thermal Decomposition of Some Cardiovascular Drugs (Telmisartane, Cilazapril and Terazosin HCL)

Thermal analysis of some antihypertensive drugs, Telmisartan, Cilazapril and Terazosin HCL was achieved. Thermogravimetry, derivative thermogravimetry and differential thermal analysis were used through the work. Thermogravimetric parameters such as activation energy, frequency factor and reaction order were calculated. The results show the stability value decrease in the order Telmisartan > Cilazapril > Terazosin. This method can be used in the quality control of pharmaceutical compounds because it is simple, fast and cheap.

辰时针刺对原发性高血压患者的降压效应

Objective:To observe the anti-hypertensive effect of time acupuncture on primary hypertension so as to provide the therapeutic regimen for the treatment of primary hypertension.Methods:A total of 120 patients with primary hypertension were randomized into a western medication group and an acupuncture-medication group,60 cases in each one.In the western medication group,levoamlodipine maleate tablets were prescribed for oral administration.In the acupuncture-medication group,on the base of the treatment as the western medication group,time acupuncture was combined in the period of a day from 7:00 a.m.to 9:00 a.m.The duration of treatment was 4 weeks in the two groups.Before and after treatment,blood pressure,serum endothelin(ET)and nitrious oxide(NO)were measured successively and the clinical therapeutic effect was evaluated.Results:(1)Blood pressure:the systolic and diastolic pressure after treatment were all lower than that before treatment in the two groups,indicating statistical differences(all P<0.05),After treatment,the systolic and diastolic pressure in the acupuncture-medication group were lower than that of the western medication group,indicating significant differences(both P<0.05).(2)ET and NO:after treatment,ET in the acupuncture-medication group was lower than the western medication group and NO was higher than the western medication group,indicating statistical differences(both P<0.05).(3)Clinical therapeutic effect:the total effective effect of anti-hypertension was 89%in the acupuncture-medication group,higher than 63%in the western medication group,indicating statistical difference(P<0.05).Conclusion:The combined treatment of western medication and time acupuncture(7:00 am to 9:00 am)achieves better effect on primary hypertension as compared with simple western medication and its anti-hypertensive effect is probably related to the decrease of ET and the increase of NO.

Calcium channel blockers improve prognosis of patients with coronavirus disease 2019 and hypertension

Background:Hypertension is considered an important risk factor for the coronavirus disease 2019(COVID-19).The commonly anti-hypertensive drugs are the renin-angiotensin-aldosterone system(RAAS)inhibitors,calcium channel blockers(CCBs),and beta-blockers.The association between commonly used anti-hypertensive medications and the clinical outcome of COVID-19 patients with hypertension has not been well studied.Methods:We conducted a retrospective cohort study that included all patients admitted with COVID-19 to Huo Shen Shan Hospital and Guanggu District of the Maternal and Child Health Hospital of Hubei Province,Wuhan,China.Clinical and laboratory characteristics were extracted from electronic medical records.Hypertension and anti-hypertensive treatment were confirmed by medical history and clinical records.The primary clinical endpoint was all-cause mortality.Secondary endpoints included the rates of patients in common wards transferred to the intensive care unit and hospital stay duration.Logistic regression was used to explore the risk factors associated with mortality and prognosis.Propensity score matching was used to balance the confounders between different anti-hypertensive treatments.Kaplan-Meier curves were used to compare the cumulative recovery rate.Log-rank tests were performed to test for differences in Kaplan-Meier curves between different groups.Results:Among 4569 hospitalized patients with COVID-19,31.7%(1449/4569)had a history of hypertension.There were significant differences in mortality rates between hypertensive patients with CCBs(7/359)and those without(21/359)(1.95%vs.5.85%,risk ratio[RR]:0.32,95% confidence interval[CI]:0.13–0.76,χ^(2)=7.61,P=0.0058).After matching for confounders,the mortality rates were similar between the RAAS inhibitor(4/236)and non-RAAS inhibitor(9/236)cohorts(1.69% vs.3.81%,RR:0.43,95% CI:0.13–1.43,χ^(2)=1.98,P=0.1596).Hypertensive patients with beta-blockers(13/340)showed no statistical difference in mortality compared with those without(11/340)(3.82% vs.3.24%,RR:1.19,95% CI:0.53–2.69,χ^(2)=0.17,P=0.6777).Conclusions:In our study,we did not find any positive or negative effects of RAAS inhibitors or beta-blockers in COVID-19 patients with hypertension,while CCBs could improve prognosis.