Cheung, BMY

Kumana, CR

Lau, CP

Leung, YH

Man, YB

Wong, LYF

Hong Kong Medical Journal

HKU Scholars Hub

Title Urotensin II in hypertensionAuthor(s) Cheung, BMY; Leung, YH; Wong, LYF; Man, YB; Lau, CP;Kumana, CRCitationThe 8th Medical Research Conference Abstracts, Hong KongMedical Journal, Hong Kong, China, 25-26 January 2003, v. 9 n. 1Supp 1, p. 24Issued Date 2003URL http://hdl.handle.net/10722/46927Rights Creative Commons: Attribution 3.0 Hong Kong License24      HKMJ Vol 9 No 1 February 2003 SupplementRandomised trial of candesartan and enalapril (RACE) in the treatment ofhypertension – final resultsBMY Cheung, CY Law, PCW Fung, KWT Tsang, KCB Tan, CR Kumana, CP Lau. University Department of Medicine,Queen Mary Hospital, Hong Kong.Introduction: The renin-angiotensin system plays an important part in the pathophysiology of hypertension. We compared two ways ofblocking the system, using an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker.Method: 22 hypertensive patients (16 men, 6 women; age 47±10 yrs) were randomised to either candesartan 8 mg or enalapril 10 mgdaily for 3 months. The dose could be doubled after 6 weeks for blood pressure control. Ambulatory blood pressure monitoring wasperformed before randomisation and before the final visit. Echocardiography was performed at randomization, 2 and 12 weeks. Flow-mediated dilatation was measured at the brachial artery to assess endothelial function. Exhaled nitric oxide was measured using anintegrated chemiluminescent system. The coefficient of variation of left ventricular mass index (LVMI), flow-mediated dilatation (FMD) andnitric oxide measurement were 7%, 5% and 3% respectively.Results: Candesartan and enalapril both significantly lowered systolic and diastolic blood pressure. This was confirmed by ambulatoryblood pressure monitoring.There were no significant differences between the treatments in their effect on LVMI and exhaled nitric oxide. Changes in LVMI corre-lated strongly with changes in the ambulatory systolic blood pressure (r=0.62, p=0.02) and diastolic blood pressure (r=0.61, p=0.02).FMD increased with enalapril but not candesartan treatment (p=0.04). Neither treatment significantly altered plasma potassium, creatinine,renin and aldosterone. Fasting blood glucose decreased significantly from 5.6±0.4 to 5.1±0.3 mmol/L in the enalapril group (p=0.01)only.Conclusions: Both drugs are efficacious in lowering blood pressure. Candesartan tended to lower blood pressure more than enalapril,which might be the result of the dosages used. Enalapril appears to have a favourable effect on blood glucose and endothelial function. Weconclude that candesartan may be used as an alternative to enalapril in the treatment of hypertension, particularly in those who areintolerant of the latter.Baseline SBP Final SBP Baseline DBP Final DBP Baseline LVMI Final LVMIcandesartan 158.2±5.7 134.5±4.3* 100.3±3.9 85.3±3.2* 139.8±12.5 134.9±11.1enalapril 159.8±4.0 145.3±6.1**  97.4±3.0 87.0±3.4* 127.3±6.4 134.5±8.0*p<0.05 vs. baseline; ** p<0.05 vs. baseline and p=0.05 vs. candesartanUrotensin II in hypertensionBMY Cheung, R Leung, LYF Wong, YB Man, CP Lau, CR Kumana. University Department of Medicine, Queen MaryHospital, Hong KongIntroduction: Urotensin II (UII) is an 11 amino acid cyclic peptide and is the most potent vasoconstrictor known.UII receptors are found in the heart and arterial vessels, including atherosclerotic plaques, suggesting that urotensinII has a role in cardiovascular diseases. UII circulates in human plasma and its plasma concentration is raised incardiac and renal failure. The role of UII in hypertension has not been investigated.Method: We studied the plasma level of UII levels in 22 hypertensive subjects (68% male, age 51±10 yrs) and 37normal controls (49% male, age 51±12 yrs ) with consent from the subjects and approval from the Ethics Committee.Plasma UII was measured using a radioimmunoassay.Results: Plasma UII was 10.6±1.4 pg/ml in normotensive controls and 21.0±3.6 pg/ml in hypertensive subjects(p=0.003). UII in men and women were not significantly different. UII did not vary significantly with age in normalhealthy subjects (r=0.09, NS) but was inversely related to age in hypertensive subjects (r=-0.35, p=0.025). In hyper-tensive subjects but not in control subjects, UII was related to diastolic blood pressure (r=0.31, p<0.05). UII is notrelated to plasma creatinine or creatinine clearance (p>0.05).Conclusions: Our results raise the possibility that this novel and potent vasoconstrictor may have an aetiologicalrole in hypertension or may be involved in the complications of hypertension. Antagonists to urotensin II might beantihypertensive agents with a novel mechanism of action.CVS-11CVS-1230      HKMJ Vol 9 No 1 February 2003 SupplementThe Heart Protection Study findings with simvastatin reanalysed by numberneeded to treatCR Kumana, BMY Cheung & IJ Lauder.† Departments of Medicine and Statistics & Actuarial Science,† The University ofHong Kong, Queen Mary Hospital, Hong KongIntroduction: Number Needed toTreat (NNT) is superior to Relative Risk Reduction (RRR) as a means of assessing clinical trial results. We therefore opted tocompare relevant RRRs and NNTs in the MRC/BHF Heart Protection Study(HPS) with Simvastatin the largest randomized trial of coronary heart disease (CHD)prevention to date, which recruited patients with prior CHD, diabetes or hypertension [HPS Collaborative Group 2002 Lancet 360:7-22].Methods: Using an Excel spreadsheet to enter event rates, NNTs and respective 95% CIs were calculated and compared with corresponding published (or derived)RRRs.Results: Respective event rates, 5 year NNTs & CIs are shown in the table.Conclusions: NNTs are more discriminating than RRRs. They confirm that the benefits of statins: are clinically significant in terms of all-cause mortality and stroke,and that for major vascular events they are similar in persons with CHD only or diabetes only and in all cholesterol level and age categories.Outcome of Interest Event Rate (%) %RRR NNTSimvastatin Placebo (95% CIs) (95% CIs)All Cause Mortality 12.9 14.7 12 (5 to 18.) 57 (37 to 128)Vascular Mortality 7.6 9.1 17 (8 to 24) 66 (44 to 134)Non-vascular Mortality 5.3 5.6 4 (* to 15) 444 (* to 117)1st Major CHD Event 8.7 11.8 26 (19 to 32) 32.7 (26 to 45)1st Stroke 4.3 5.7 24 (14 to 33) 73 (50 to 131)Revascularisaton 9.1 11.7 22 (15 to 29) 39 (29 to 58)1st Major Vascular Event<5.0 17.7 23.1 23 (12 to 33) 19 (13 to 35)Total Cholesterol (mmol/L) ≥5.0 <6.0 16.9 24.5 23 (15 to 30) 18 (13 to 27)≥6.0 21.6 26.8 19 (12 to 26) 19 (14 to 30)<65 16.9 22.1 23 (16 to 30) 19 (15 to 28)Age   (years) ≥65 <70 20.9 27.2 23 (14 to 32) 16 (11 to 26)≥70 23.6 28.7 18 (9 to 26) 20 (14 to 36)Prior CHD only 16.8 22.5 25 (17 to 33) 18 (13 to 26)Prior Diabetes only 13.8 18.6 26 (13 to 37) 21 (14 to 40)Prior CHD + Diabetes 33.4 37.8 11 (* to 24) 23 (12 to *)* Denotes a negative value indicating an increased event rate in the treated group, renderng further analysis inappropriate; 1st major coronary event = non-fatal MIor CHD death; Revascularisation = coronary and non-coronary bypass and angioplasty; 1st major vascular event = 1st major coronary event, stroke or revascularisationCVS-23CVS-24 Endotoxin increases adrenomedullin expression in heart, lung and mesentericarteryYY Li, F Tang1 and BMY Cheung2Department of Physiology1 and Department of Medicine,2 The University of Hong KongIntroduction: Previous studies have shown that the circulating levels of adrenomedullin (AM) are elevated duringinflammation. The levels of AM and its messenger RNA (mRNA) in various tissues during the time course ofinflammation remain to be determined.Method: Inflammation was induced in rats by intraperitoneal injection of lipopolysaccharide (LPS, 10mg/kg). Thetissues were harvested at 0, 1, 3 and 6 hours after LPS administration. Tissue levels of AM were determinedby radioimmunoassay. The gene expression levels of AM were determined by solution hybridization-RNaseprotection assay of preproAM mRNA levels.Results: PreproAM mRNA levels were increased in mesenteric artery and right atrium at 1 hour, in the leftventricle and the lung at 3 and 6 hours and in the right ventricle at 6 hours, after LPS injection. AM levels in themesenteric artery were increased at 1, 3 and 6 hours and at 3 and 6 hours in the lung after LPS injection.Conclusions: There is an increase in AM release in the lung, so it may be an important organ for AM secretion inthe septic state. However, the response of the lung and the mesenteric artery to LPS in terms of AM secretionappears to be different.

Urotensin II in hypertension

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Urotensin II in hypertension

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