Effects of the angiotensin II receftor blocker EXP 3174 on renal glomerular hemodynamics in the dog

AJR-APRIL1995-VOL,8, NO.4, PART 2

POSTERS: ACE Inhibition and Renin/Angiotensin Antagonists .183A

C34'

C33 EFFICACY OF MOEXIPRIL AS ADD·ON THERAPY TO HYDROCHLOROTHIAZIDE IN PATIENTS WITH MODERATE TO SEVERE HYP£:F:TENSION K Dickstein,M Stlmpel+;HjertelagetResearch Foundation, Stavanger, Norway; +Clinical Research, Schwarz Pharma AG, Monhelm,Germany. Moexipril Is an orally administered prodrug of a nonsulrhydryl·contalnlng,nonpeptlde angiotensin converting enzyme (ACE) Inhibitor. This study was designed to evaluate the efficacy of three dose levels of Moexlpril versus placebo as add-on thera;>y to HydrochlorothlF.lZide (HCT:?) in patientswith uncomplicatedmoderate to severe hypertension. Aftera 4·week treatmentwith HCTZ 25 mg once daily 200 patients (aged 25·7t. years) with sitting diastolic blood pressure between 95-114 mmHg were randomized in a parallel, double·"Hnd fashion to placebo or Moexipril 3.75 mg, 7.5 mg or 15mg. Bloodpressurewas measuredat 22·26 h postdoseat biweeklyvisitsand at 1, 2, 3 and 4 h postdoseafterthe firstdose ofdouble-blindmedication. Atendpoint,adjustedmean reductionsfrom baselineSDBP were 8.4,8.8 and 8.9 mmHg In the Moexlpril3.75, 7.5 and 15mg groups,respectively,ascomparedwitha reductionof 4.6 mmHg inthe placebogroup( p~O.003). The differences In systoJic blood pressure reductions were statistically significantInfavourofeach ofthe Moexiprilgroupsoverthe placebo group at all trough time points. Adjusted mean changes in sittingsystolicblood pressurewere 10.9, 12.0 and 11.7 mmHg, respectively,ascomparedwith a reduction of 0.6mmHg inthe placebogroup(p
Key Words;

Moexipril • Hydrochlorothiazide - Hypertension

C35 BrFBCT8 01" THB ANGIOTBNSIN I:t RBCBFTOR BLOCKBR BXP 3114 ON RENAL GLOHBRULAR HBHODYNAH1S:S IN TIll DOG. J •Heller" H.J.

Kramer 2, V. Horacek\ 'Inst clin Exp Med, Praque, CR, and 2Renal Section, Medical Policlinic, university of Bonn, Germany. EXP 3174, the active metabolite of the AII receptor antagonist LosartanR, was infused intrarenally in anesthetized dogs kept on a low-salt diet (0.3 mmol NaCl/kg Iday). The dose of 30 jjg/min/kg blocked completely the vasoconstrictor response to l.r.a. AIl (10 ng/kg BW). A rise in renal blood flow (RBF) by 15% froDI 4.41 ± 0.22 to 5.11 ± 0.23 was accompanied by a smaller but significant rise in GFR by 8% from 0.61 ± 0.03 to 0.66 ± 0.03 ml/min/g KW and in filtration fraction by 7%. Very similar changes were seen on the single nephron leveL Urine H:lW rate and Na, K and urea excretion we:r'e increased. There was a small Increase in hydraulic pressure in perituPvla~ ~~pillaries and proximal convolutions wit~ a slight decrease in glomerular capilla;ry pressure. These resulted in a decreaJ.e in effective filtration pressure fro~ 12.64 ± 0.44 to 8.59'± 0.54 mmHg. Ultrafiltration coefficient, Kfl increased significantly from 4.82 ± 0.21 to 7.72 ± O. 32 ~l/min/mmHg. The decrease in arteriolar resistance of 17% was more 'pronounced in the efferent (-26%) than afferent (-11%) arteriole. Thus, effects of EXF 3174 ressemble those of saralasin. EXP 3174 does not exhibit the bradykininmediated effects of ACE-inhibition which we previously demonstrated in the presence of HOE-140, a specific B2-antagonist. Keywords:

A II, EXP 3174, dog, glomerUlar hemodynamics

MOEXIPRIL VERSUS CAPTOPRIL IN PATIENTS WITH MILD TO MODERATE HYPERTENSION M $tlmpel+ ,lie: Loh; +Clinlcal Research, Schwarz Pharma AG, Monheim,Germany;Ventura Heart Institute,Thousand Oaks, USA MoexfprilIs a new, long actingACE inhibitor.Inconuastto Captopril• the prototypeof ACE Inhibitors• MoexlprilIs a pro-drugof thepharmacologicallyactive agent Moexip,.n\it. The objectiveof this studywas to compare the efficacy, safetyand tolerabilityofMoexlprlland Captoprilinthetreatment ofpatientswith mild tomoderatehypertensionduring a 12-week period. Patients with a sitting diastolicblood pressure (SDep) of 95- 114 mmHg, lncluslve,were randomizedin a2:1 ralioto receiveMOE:!xipriI7.5mg oncedailyorCaptoprll25mg twice daily. Dose of W."exipril and Captoprilwas increased to 15 mg and 50 mg, respectivElly,if thepatient'sS08P remained > 90 mm Hg after sixweeks of treatment. Blood pressurewas measured10-14 h postdoseat biweeklyvisits and 1 and 2 h after firstapplicationof active drug and after titrationof cose- ifapplicable. After6 weeks of double-blindtreatment,the adjustedmean reductionfrom baselinein SDepwas significantly(1'=0.049) greater in the Moexipril group (9.0 mmHg) than in the Captopril group (6.6 mm Hg). At the end of the study adjusted mean reductions in SOBP were comparable between the two groups (9.8 mmHg vs. 8.7 mmHg). Moexipril was more effective than Captopril in reducing sitting systolicblood pressure after 6 and 12 weeks of treatment. Adverse experiences (headache, cough, dizzinessand fatigue) occuredat similarfrequencesin the Moexiprilaswell asinthe Captoprilgroup. The data indicatethat Moexiprilin dosages of 1.5and 15 mg once daily is asefficaciousas CaptopriJtwice daily to lower blood pressure in patients with mild to moderate hypertension. KeyWords:

Moexipril

Captopril

Hypertension

C36 CAN DYSLIPIDEMIA AND REDUCED INSULIN (INS) RffilSTANCE BE IMPROVED BY MEDICATIONS FOR HYPERTENSION? COMPARISON AMONG NIFEDIPINE (N), I.ACIDIPINE ru, CAPTOPRIL AND TCV·l14 (A NEW ANGIOTENSIN II RECEPTOR ANTAGONIST; T). K:Masuo·, H. Mikami*, T. Ogihara*, and M.l. TuckI *. Department of Geriatric Medicine, Osaka University Medical School, Osaka, Japan, and I UCLA School of Medicine, Los Angeles, CA. To evaluate the differences In ameliorative effects on dyslipidemla and reduced INS sensitivity of medications for hypertension (HT) we compared glucoseand llpld metabolism in young, non-obese hypertensive patients (EH. WHO HI) before and after medicationsby N, L, C, and T for 1 yr. In each of the 20 patients treated by N, L, C, and T (2 of which were treated by T and all of whomwere controlled normotensive subjects (NT)). age and BMI were strictly matched (Sl.±.3, 54±.5, 52±4, 56±!, 53.±.3 yrs, 22.5iO.2, 23.0±0.8, 22.51.0.1, 22.7±O.2. 22.8±0.3kg/rn-). Fasting blood glucose (BG), plasma INS level, total cholesterol (T-ch), triglyceride (TG), HDL-, VLOL-, LOLch were measured after more than 12 hrs fasting before and after medication for I yr. EH had significantly greater fasting INS, T-ch,TG and VLDL-ch than NT before medication. However, L improved dyslipldemia and reduced INS sensitivity slightly better than N (INS:P
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Key Words: dyslipidemia, insulin resistance, calcium antagonist. ACE-Inhibitor. Ang II rec. antag,