trandolapril and Cough

The effects of 2 fixed antihypertensive combination drugs on blood pressure and aortic elastic properties were compared in 2 parallel groups. Twenty-six patients for 6 months received a calcium antagonist plus ACE inhibitor (verapamil SR 180 mg/trandolapril 1 mg (Vera/Tran)) and 25 patients a beta-adrenoceptor antagonist plus diuretic (metoprolol 100 mg/hydrochlorothiazide 12.5 mg (Meto/HCTZ)). In addition to blood pressure (SBP, DBP), carotidofemoral pulse wave velocity (PWV) was assessed non-invasively. Total peripheral resistance (TPR) was determined from cardiac output derived by electrical impedance cardiography. Sitting DBP decreased for -14.4 mmHg following Vera/Tran compared with -9.2 mmHg following Meto/HCTZ (p = 0.02 for difference between treatments). Blood pressure was normalized (i.e. DBP < 90 mmHg) in 69% of patients with Vera/Tran and in 52% with Meto/HCTZ. PWV was lowered with Vera/Tran to a higher extent than with Meto/HCTZ (differences between group means -0.46 to -0.98 m/sec, statistically not significant). Vera/Tran induced a decrease in TPR of about 15% of baseline values, whereas Meto/HCTZ showed no influence. Treatment-related adverse events following Meto/HCTZ were bradycardia and associated symptoms; following Vera/Tran these were cough and edema in 1 case each. In the Meto/HCTZ group, there were more withdrawals/drop-outs (9/25) than in the Vera/Tran group (2/26). The somewhat more intense reduction in PWV with Vera/Tran is indicative of an increase in aortic elastic properties associated with the more potent decrease in BP. In the present study, the combination of calcium antagonist plus ACE inhibitor was found to be an effective and well tolerated antihypertensive regimen and in these respects appears to have some advantages compared with a combination of beta-blocker plus diuretic.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Aorta; Blood Pressure; Bradycardia; Calcium Channel Blockers; Cough; Diuretics; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Indoles; Male; Metoprolol; Middle Aged; Sodium Chloride Symporter Inhibitors; Verapamil

Persistent dry cough is well known as the most common side-effect of angiotensin-converting enzyme (ACE) inhibitors. We examined the relationship between a cough and ACE gene polymorphism, plasma bradykinin (BK), substance P (SP) and ACE inhibitor concentrations in patients with hypertension or chronic nephritis. First, ACE genotyping was carried out in 96 patients, 42 with coughs and 54 without coughs, which had been treated with various kinds of ACE inhibitors. However, no significant difference in the ACE genotypes was observed between the two groups. Second, the plasma concentrations of BK, SP and ACE inhibitor were measured in 12 patients, which were treated with trandolapril at a daily dose of 1 mg for 4-33 weeks. In 3 patients, the cough was induced during the trandolapril therapy, while it was induced not in 9 patients. The plasma levels of BK and SP did not significantly change after trandolapril administration in the patients with and without coughs. Between the two groups, there were no significant differences in the plasma levels of BK and SP either before or after the trandolapril therapy. Also the plasma concentrations of trandolapril and trandolaprilat, the active metabolite of trandolapril, did not significantly differ between the two groups. These results suggest that there is no significant relationship between the ACE inhibitor-induced cough and ACE gene polymorphism, plasma BK, SP and ACE inhibitor concentrations in patients with hypertension or chronic nephritis.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Chronic Disease; Cough; Female; Humans; Hypertension; Indoles; Male; Middle Aged; Nephritis; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Substance P

We examined the effect of trandolapril ((-)-(2S, 3aR, 7aS)-1-[(S)-N-[(S)-1-ethoxycarbonyl-3- phenylpropyl]alanyl]hexahydro-2-indolinecarboxylic acid), a potent angiotensin converting enzyme (ACE) inhibitor, on the number of capsaicin-induced coughs in guinea pigs and compared it with that of enalapril. Chronic treatment with enalapril, at a dose of 3 mg/kg, p.o., significantly enhanced the number of capsaicin-induced coughs. Chronic treatment with trandolapril, at doses of 1 and 3 mg/kg, p.o., slightly enhanced the number of capsaicin-induced coughs. However, there were no significant differences in the number of capsaicin-induced coughs between trandolapril-treated and vehicle-treated animals. These results suggest that cough induced activity, one of the most serious side effects associated with chronic treatment with ACE inhibitors, of trandolapril is relatively lower than that of enalapril.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Capsaicin; Cough; Enalapril; Guinea Pigs; Indoles; Male