The present study was designed to examine whether Ramipril (an inhibitor of angiotensin-converting enzyme) affected spontaneous hypertension-induced injury of cerebral artery by regulating connexin 43 (Cx43) expression. Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were randomly divided into WKY, WKY + Ramipril, SHR, and SHR + Ramipril groups (n = 8). The arterial pressure was monitored by the tail-cuff method, and vascular function in basilar arteries was examined by pressure myography. Hematoxylin-eosin (HE) staining was used to show vascular remodeling. The expression and distribution of Cx43 was determined by using immunofluorescence and immunohistochemistry analysis. The protein and mRNA levels of Cx43 were examined by Western blot and real-time PCR analysis, respectively. The results showed that chronic Ramipril treatment significantly attenuated blood pressure elevation (P < 0.01, n = 8) and blood vessel wall thickness in SHR (P < 0.01, n = 8). The cerebral artery contraction rate in the SHR group was higher than that in the WKY group (P < 0.05, n = 8). The cerebral artery contraction rate in the SHR + Ramipril group was lower than that in the SHR group (P < 0.05, n = 8). Pretreatment with 2-APB (Cx43 non-specific blocker) or Gap26 (Cx43 specific blocker) significantly decreased the vasoconstriction rate, while pretreatment with AAP10 (Cx43 non-specific agonist) significantly increased the vasoconstriction in the SHR + Ramipril group (P < 0.05, n = 8). In addition, the expression of Cx43 mRNA and protein in cerebral arteries of SHR group was higher than that of WKY group (P < 0.05, n = 8). The mRNA and protein expression of Cx43 in cerebral arteries of SHR + Ramipril group was significantly lower than that of SHR group (P < 0.05, n = 8). These results suggest that Ramipril can down-regulate the expression of Cx43 mRNA and protein in cerebral arterial cells of SHR, lower blood pressure, promote vasodilation, and improve arterial damage and vascular dysfunction caused by hypertension.
Animals ; Blood Pressure ; Cerebral Arteries ; drug effects ; metabolism ; Connexin 43 ; metabolism ; Hypertension ; drug therapy ; Ramipril ; pharmacology ; Random Allocation ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Vascular Remodeling

No abstract available.
Antihypertensive Agents ; Hypertension ; Blood Pressure ; Myocardial Ischemia ; telmisartan ; Ramipril ; Risk Factors

Recently, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure (BP) trial enrolled 4733 participants with type 2 diabetes and randomized them to a target systolic blood pressure (SBP) of less than 120 mm Hg or 140 mm Hg. Despite the significant difference in the achieved SBP, there was no significant difference in the incidence of primary outcomes. Based on this evidence, the target SBP for diabetics has been revised in the majority of major guidelines. However, there is a steeper association between SBP and stroke in Asians than other ethnicities, with stroke being the leading cause of cardiovascular mortality. This suggests that target BP in the Asian region should be tailored towards prevention of stroke. In the ACCORD study, the intensive BP treatment was associated with significant reductions in both total stroke and non-fatal stroke. The results from the ACCORD study are supported by a subgroup analysis from the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) study, which showed that, in diabetic patients, the risk of stroke continues to decrease to a SBP value of 115 mm Hg with no evidence of J curve. As diabetes is highly associated with underlying coronary artery disease, there is a justified concern for adverse effects resulting from too much lowering of BP. In a post hoc analysis of 6400 diabetic subjects enrolled in the International Verapamil SR-Trandolapril (INVEST) study, subjects with SBP of less than 110 mm Hg were associated with a significant increase in all-cause mortality. In the ONTARGET study, at any levels of achieved SBP, diastolic blood pressure (DBP) below 67 mm Hg was associated with increased risk for cardiovascular outcomes. As such, a prudent approach would be to target a SBP of 130–140 mm Hg and DBP of above 60 mm Hg in diabetics with coronary artery disease. In conclusion, hypertension, in association with diabetes, has been found to be significantly correlated with an elevated risk for cardiovascular events. As the association between stroke and BP is stronger in Asians, compared to other ethnicities, consideration should be given for a target BP of 130/80 mm Hg in Asians.
Asian Continental Ancestry Group* ; Blood Pressure* ; Coronary Artery Disease ; Humans ; Hypertension ; Incidence ; Mortality ; Ramipril ; Stroke ; Verapamil

BACKGROUNDCombination of angiotensin-converting enzyme inhibitors and calcium channel blockers has been successfully used in the antihypertensive therapy for many years. Fixed dose combinations of ramipril/amlodipine have a benefit effect for patients to achieve target blood pressure (BP). This study aimed to assess the efficacy and safety of fixed dose combinations of ramipril and amlodipine (Egiramlon®) in hypertensive diabetic patients.

METHODSHypertensive diabetic patients who were enrolled into the RAMONA trial were included in this open, prospective, Phase IV observational clinical study. Patients had mild-to-moderate hypertension and failed to reach target BP levels through their previous therapy. During the four months of observation, patients took part in three visits (1st day = visit 1, 1st month = visit 2, and 4th month = visit 3) where they received a fixed dose combination of 5/5, 5/10, 10/5, or 10/10 mg ramipril/amlodipine, respectively, with the possibly required dose titrations, based on the decision of their attending physician. Target BP for diabetic patients was <140/85 mmHg. BP levels were measured in all visits, by taking two readings at 2-min interval. Laboratory tests including full blood count, renal function test, electrolytes, blood glucose, serum cholesterol, uric acid, triglycerides, liver function test, creatinine kinase, and midstream urinalysis were performed at visit 1 and visit 3.

RESULTSThe 6423 patients completed the study. Among these patients, 1276 (19.9%) patients suffered from type 2 diabetes mellitus. The mean age of these diabetic patients was 64.2 ± 10.0 years; 707 (55.4%) patients were males. Target BP was achieved by 891 (69.8%) of diabetic patients at visit 3 (primary endpoint). BP decreased from 157.5/91.3 ± 9.6/7.6 mmHg (visit 1) to 130.9/79.6 ± 7.4/5.8 mmHg (visit 3). As for the secondary endpoint of the study, total cholesterol decreased from 5.50 ± 1.13 mmol/L (visit 1) to 5.20 ± 0.95 mmol/L (P = 0.000), low-density lipoprotein cholesterol decreased from 3.20 ± 0.93 mmol/L to 3.00 ± 0.77 mmol/L (P = 0.000), triglyceride decreased from 2.20 ± 1.14 mmol/L to 2.00 ± 1.97 mmol/L (P = 0.000), while high-density lipoprotein cholesterol increased from 1.30 ± 0.42 to 1.35 ± 0.30 mmol/L (P = 0.001) until the end of the 4th month (visit 3). Fasting blood glucose of the hypertensive diabetic patients decreased from 7.20 ± 1.88 mmol/L to 6.70 ± 1.38 mmol/L (P = 0.000), while HbA1c decreased from 7.90 ± 1.78% to 7.60 ± 1.83% (P = 0.000). Various fixed dose combinations of ramipril/amlodipine were well tolerated and no adverse event related to the use of the medicine has appeared.

CONCLUSIONSThe fixed dose combination of ramipril/amlodipine was effective in hypertensive diabetic patients who failed to reach target BP previously.

Aged ; Amlodipine ; administration & dosage ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; therapeutic use ; Antihypertensive Agents ; administration & dosage ; therapeutic use ; Blood Pressure ; drug effects ; Diabetes Mellitus, Type 2 ; drug therapy ; Female ; Humans ; Hypertension ; drug therapy ; Male ; Middle Aged ; Ramipril ; administration & dosage ; therapeutic use

A 6 year-old, spayed female, Maltese dog was presented with precordial thrill and mild coughing. Thoracic auscultation revealed a grade V/VI systolic murmur with maximal intensity over the left apex characterized by musical murmur. Echocardiography revealed mild myxomatous degeneration of mitral valve and ruptured chordae tendineae. Musical murmur was produced due to the vibration of ruptured piece of chordae tendineae along with regurgitant flow. After treatment with furosemide and ramipril, clinical signs resolved and precordial thrill reduced. This case report describes typical clinical signs and phonocardiogram of musical murmur in a dog with acute chordae tendineae rupture.
Animals ; Auscultation ; Child ; Chordae Tendineae* ; Cough ; Dogs* ; Echocardiography ; Female ; Furosemide ; Humans ; Mitral Valve ; Music* ; Ramipril ; Rupture* ; Systolic Murmurs ; Vibration

BACKGROUNDAliskiren is a novel blood pressure-lowering agent acting as an oral direct renin inhibitor. The aim of this study was to assess the effect of aliskiren on arterial stiffness, compared with that of ramipril in mild to moderate essential hypertensive patients.

METHODSFollowing a two week placebo run-in period, patients with a mean sitting diastolic blood pressure (ms-DBP) ≥ 95 and < 110 mmHg (1 mmHg = 0.133 kPa), and a mean sitting systolic blood pressure (ms-SBP) < 180 mmHg were randomly allocated to treatment with aliskiren (150 mg/d, n = 20) or ramipril (5 mg/d, n = 20) for eight weeks. Blood pressure, plasma renin activity, and the brachial-ankle pulse wave velocity (ba-PWV) were measured before and after eight weeks of treatment.

RESULTSEight weeks of treatment significantly decreased systolic blood pressure and diastolic blood pressure in both the aliskiren group and ramipril group. The hypotensive effect did not differ between the two groups. Plasma renin activity decreased after aliskiren treatment and increased after ramipril treatment. There was no significant difference in baseline ba-PWV between the aliskiren and ramipril groups (P = 0.892). The ba-PWV was significantly reduced in both the aliskiren group (1535 (1405 - 1666) vs. 1464 (1360 - 1506) cm/s) (P < 0.01) and the ramipril group (1544 (1433 - 1673) vs. 1447 (1327 - 1549) cm/s) (P < 0.01). No statistically significant difference was found in the decline of ba-PWV between the two groups (P = 0.766).

CONCLUSIONSThe current study revealed that aliskiren (150 mg/d) could ameliorate arterial stiffness and its effect was similar to ramipril (5 mg/d) in mild to moderate hypertensive patients, indicating that in addition to lowering blood pressure, aliskiren had beneficial effect on vascular protection.

Adult ; Amides ; therapeutic use ; Antihypertensive Agents ; therapeutic use ; Female ; Fumarates ; therapeutic use ; Humans ; Hypertension ; drug therapy ; physiopathology ; Male ; Middle Aged ; Ramipril ; therapeutic use ; Vascular Stiffness ; drug effects

Amides ; therapeutic use ; Antihypertensive Agents ; therapeutic use ; Female ; Fumarates ; therapeutic use ; Humans ; Hypertension ; drug therapy ; Male ; Ramipril ; therapeutic use ; Vascular Stiffness ; drug effects

BACKGROUNDThe results from the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) indicated that the angiotensin-receptor blocker telmisartan was not inferior to the angiotensin-converting-enzyme inhibitor ramipril in reducing the composite endpoint of cardiovascular death, myocardial infarction, stroke or hospitalization for congestive heart failure in high-risk patients, and telmisartan was associated with slightly superior tolerability. The combination of the two drugs was associated with more adverse events without an increase in benefit. This study aimed to analyze the data from ONTARGET obtained from a subgroup of patients enrolled in China and to evaluate the demographic and baseline characteristics, the compliance, efficacy, and safety of the different treatment strategies in randomized patients in China.

METHODSA total of 1159 high-risk patients were randomized into three treatment groups: with 390 assigned to receive 80 mg of telmisartan, 385 assigned to receive 10 mg of ramipril and 384 assigned to receive both study medications. The median follow-up period was 4.3 years.

RESULTSThe mean age of Chinese patients was 65.6 years, 73.6% of patients were male. The proportion of patients with stroke/transient ischemic attacks at baseline in China was two times more than the entire study population (47.7% vs. 20.9%). In Chinese patients the proportion of permanent discontinuation of study medication due to cough was 0.5% in the telmisartan group, which was much less than that in the combination or the ramipril group. There were no significant differences in the incidence of primary outcome among three treatment groups of Chinese patients. More strokes occurred in Chinese patients than in the entire study population (8.5% vs. 4.5%). Greater systolic blood pressure reduction (-9.8 mmHg), and more renal function failure were noted in the combination treatment group than in the ramipril or telmisartan group (2.6% vs. 1.6% and 1.0%).

CONCLUSIONSThere was no evidence that the results of ONTARGET differed between Chinese patients and the entire study population with respect to the incidence of primary outcome, particularly safety. Compliance with study medications was good. The evidence from ONTARGET indicated that the treatment strategies in ONTARGET were applicable to patients in China.

Aged ; Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Benzimidazoles ; administration & dosage ; adverse effects ; therapeutic use ; Benzoates ; administration & dosage ; adverse effects ; therapeutic use ; China ; Drug Therapy, Combination ; Female ; Heart Failure ; drug therapy ; Humans ; Male ; Middle Aged ; Ramipril ; administration & dosage ; adverse effects ; therapeutic use

BACKGROUND: The aim of this study was to compare the antihypertensive effect of S-(-)-amlodipine nicotinate with ramipril in patients with essential hypertension. METHODS: Total 138 patients (54.5 +/- 10.5 years, 69 males) were enrolled in this study between 2008 and 2010. Amlodipine 2.5 mg or ramipril 2.5 mg was treated once in a day for 8 weeks. Epidemiologic analysis was performed in intend-to-treat (ITT) group. Efficacy analysis was performed in the differences of diastolic blood pressure in study groups. Abnormal reactions were divided with severities and drug-relationship. RESULTS: The change of diastolic blood pressures were more prominent with -12.7 +/- 7.02 mm Hg in amlodipine group, and -9.6 +/- 7.38 mm Hg in ramipril group (p = 0.023). The change of systolic blood pressures was higher in amlodipine group with -18.1 +/- 7.91 mm Hg, and -14.3 +/- 11.96 mm Hg in ramipril group (p = 0.047). Blood pressure normalization rates were 81.3% (48 of 59 patients) in amlodipine group, and 61.4% (35 of 57 patients) in ramipril group (p = 0.017). Abnormal reaction occurred in 5.8% (4 of 68 patients) of amlodipine group and 14.2% (10 of 70 patients) of ramipril group (p = 0.102). The most frequent abnormal reaction was respiratory symptom. CONCLUSIONS: S-Amlodipine-Nicotinate was more effective than ramipril in hypertensive patients without significant abnormal reaction.
Amlodipine ; Blood Pressure ; Humans ; Hypertension ; Niacin ; Ramipril

BACKGROUND: Pulmonary hypertension is considered as a poor prognosis factor in patients with chronic obstructive pulmonary disease (COPD). There has been reported brain natriuretic peptide (pro-BNP) is related with increased right ventricular (RV) workloads. However, there are few studies that evaluate the relationship between BNP and pulmonary arterial pressure (PAP), RV function and St. George Respiratory Questionnaire (SGRQ) score in patients with COPD, and the effects of angiotensin converting enzyme inhibitor (ACEI) on these parameters. METHODS: Pulmonary function test, echocardiography, blood BNP, and SGRQ score were evaluated in stabilized moderate degree COPD patients (FEV1/FVC<70%, 50%< or =FEV1<80%) aged 45 years and over, without worsening of symptoms within recent 3 months. After treating with ramipril 10 mg for 3 months, the same evaluation was repeated. RESULTS: Twenty-two patients were included in this study. BNP was significantly correlated with PAP (Pearson coefficient rho=0.51, p=0.02), but not with RV ejection fraction (EF) and predicted FEV1%. The values for predicted FEV1% showed significant correlation with SGRQ total score and activity score, but not with BNP or PAP. After ramipril treatment, PAP showed significant decrease (42.8+/-8.1 vs. 34.5+/-4.5 mm Hg p=0.0003), tricuspid annular plane systolic excursion significant increase (21.5+/-3.3 vs. 22.7+/-3.1 mm p=0.009). BNP showed a tendency to decrease without statistical significance (40.8+/-59.6 vs. 18.0+/-9.1 pg/mL p=0.55). SGRQ scores showed no significant change. CONCLUSION: BNP showed significant correlation with resting PAP, which means BNP could be used as markers for pulmonary hypertension. Treatment with ACEI didn't show significant change in the level of BNP, while pulmonary hypertension and RV function were improved.
Aged ; Angiotensin-Converting Enzyme Inhibitors ; Angiotensins ; Arterial Pressure ; Brain ; Echocardiography ; Humans ; Hypertension, Pulmonary ; Natriuretic Peptide, Brain ; Peptidyl-Dipeptidase A ; Prognosis ; Pulmonary Disease, Chronic Obstructive ; Surveys and Questionnaires ; Ramipril ; Respiratory Function Tests