Hemodynamic and Biochemical Changes after Chronic Administration of Cilazapril to Hypertensive Patients

Abstract

The study describes the changes in basic hemodynamic parameters after long-term antihypertensive therapy with cilazapril - a new ACE inhibitor lacking a sulfhydryl group - in hypertensive patients and the drug effects on renal function, glucose tolerance and lipid metabolism. 30 patients (18 males, 12 females, mean age: 53.3 ± 18 years) with mild to moderate essential hypertension were studied. The following determinations were performed in patients, before and after 4.5 months of cilazapril monotherapy at a dose of 5 mg/24 h: (a) antihypertensive action of the drug (arterial pressure at rest and during a 24-hour recording); drug effects on left ventricular (LV) mass index; its contractility indexes (%FS, EF) and the left atrial emptying index were studied by means of echocardiography; plasma insulin concentration during oral glucose tolerance tests, in the fasting state, after the administration of 75 g glucose per os, as well as the changes in the insulinogenic index and the 6-keto-PGF_1α/TXB₂ ratio, and drug effect on renal function (urea, creatinine, uric acid, plasma electrolytes), blood lipid profile (total cholesterol, triglycerides, HDL-CH) and serum transaminases. Long-term drug administration exhibits an effective antihypertensive action, without causing reflex tachycardia and also reduces the LV mass index without affecting its EF, while improving its diastolic function. It does not significantly affect the various biochemical parameters, and achieves glucose regulation, both in the fasting state and after glucose loading, with a decrease in the insulinogenic index, and simultaneously increases the 6-keto-PGF_1α/TXB₂ ratio. The existence of a direct cause-effect relationship between the changes in the above hormone systems is possible.

Antihypertensive agents, insulin sensitivity, and new-onset diabetes

“…Similarly, enalapril significantly increased clampderived IS in hypertensive type 2 diabetic patients [14]. Cilazapril was also shown to significantly improve IS estimated with the insulinogenic index [33] or a modified insulin suppression test [34], and fosinopril was found to significantly decrease the HOMA-IR index in hypertensive patients [35]. In other cases, captopril [36], enalapril [30,37,38], and trandolapril [39] were not found to significantly change IS, but some of these studies could be limited by small sample sizes and the relevant findings should be interpreted carefully, as mentioned above [31].…”

Η Επιδραση Της Ενδογενους Ινσουλινης Στην Ομοιοστασια Των Ηλεκτρολυτων Στην Ιδιοπαθη Αρτηριακη Υπερταση

“…Στη μελέτη μας, ο λόγος της ινσουλίνης του ορού σε μυ/ml προς τη σύστοιχη τιμή της γλυκόζης του ορού σε mg/dl για κάθε στιγμιότυπο, αλλά και ο λόγος της ολικής ανταπόκρισης της ινσουλίνης προς την ολική αντα πόκριση της d-γλυκόζης, στο χρονικό διάστημα του δίωρου της μελέτης, α ποτέλεσαν τον δείκτη ινσουλινογένεσης (insulinogenic index), που έχει χρησιμοποιηθεί σε αρκετές μελέτες ελληνικές και ξένες 326 " 330 . Ο δείκτης αυτός αποτελεί μέσο μελέτης της αντίστασης ή της ευαισθησίας στην ιν σουλίνη.…”