Drugs online research references
J Mol Cell Cardiol. 1998 Dec;30(12):2683-94.
Sub-antihypertensive doses of ramipril normalize sarcoplasmic reticulum calcium ATPase expression and function following cardiac hypertrophy in rats.
Boateng SY, Seymour AM, Bhutta NS, Dunn MJ, Yacoub MH, Boheler KR.
Imperial College School of Medicine, Department of Cardiothoracic Surgery, London, UK.
We examined the hypothesis that the angiotensin converting enzyme inhibitor ramipril at sub-antihypertensive concentrations could improve sarcoplasmic reticulum (SR) CaATPase expression and function in compensated hypertrophied rat hearts. Five weeks after abdominal aortic constriction, rats received a daily dose (50 micrograms/kg/day) of ramipril or vehicle for 4 weeks. Cardiac angiotensin-converting enzyme (ACE) activity increased with cardiac hypertrophy (CH) but returned to normal following ramipril treatment. SR CaATPase protein levels and activity decreased with CH (P < 0.05) and were normalized following ramipril treatment (P < 0.05 for protein and activity). No change in phospholamban (PLB) protein levels could be demonstrated between any of the groups. In contrast, ramipril treatment specifically increased control SR CaATPase and PLB mRNA levels by > 60% (P < 0.01) and > 30%, respectively. In the hypertrophied group, SR CaATPase increased by 35% (P < 0.05 n = 6) after ramipril treatment. Calsequestrin mRNA levels were unaffected by ramipril administration. In conclusion, ramipril normalizes SR CaATPase protein expression and function in pressure-overloaded and compensated CH. The effects of ramipril are however multifaceted, affecting RNA and protein expression differentially.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9990539&dopt=Abstract
Eur J Pharmacol. 1993 Oct 5;242(3):237-43.
Effects of one-hour and one-week treatment with ramipril on plasma and renal brush border angiotensin converting enzyme in the rat.
Michel B, Stephan D, Grima M, Barthelmebs M, Imbs JL.
Institut de Pharmacologie, URA DO589 CNRS, Universite Louis Pasteur, Strasbourg, France.
Prolonged treatment with an angiotensin converting enzyme inhibitor produces an induction of plasma angiotensin converting enzyme. Induction of angiotensin converting enzyme in tissues during prolonged treatment with an angiotensin converting enzyme inhibitor is less well documented. We compared the effects of 1 h and 1 week treatment with ramipril (0.1, 0.3, 1 mg/kg) on angiotensin converting enzyme activity in the plasma, renal cortex and renal brush border membrane of Wistar rats. As an increase in activity could be masked by the inhibition due to the presence of ramiprilat which is the active form of ramipril, we eliminated the ramiprilat present in renal cortex homogenates with EGTA during brush border preparation. The 1-h treatment with ramipril induced a dose-dependent inhibition of plasma and renal cortex angiotensin converting enzyme activity. The 1-week treatment with ramipril produced an increase in plasma angiotensin converting enzyme activity, whereas renal cortex angiotensin converting enzyme activity decreased. The decrease in angiotensin converting enzyme activity persisted in the brush border membrane after elimination of residual ramiprilat with EGTA. Our results show that prolonged ramipril treatment produces opposite responses in plasma and renal cortex angiotensin converting enzyme activity, suggesting that plasma and epithelial angiotensin converting enzymes are subject to specific local regulatory factors.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8281988&dopt=Abstract
Br J Pharmacol. 1998 Jan;123(2):195-204.
Influence of dietary salts on the cardiovascular effects of low-dose combination of ramipril and felodipine in spontaneously hypertensive rats.
Mervaala EM, Malmberg L, Teravainen TL, Laakso J, Vapaatalo H, Karppanen H.
Institute of Biomedicine, Department of Pharmacology and Toxicology, University of Helsinki, Finland.
1 In spontaneously hypertensive rat (SHR) we examined over a 4-week period the influence of control low sodium diet, common salt-enriched diet (sodium chloride 6% of the dry weight of the chow) and a novel mineral salt-enriched diet (potassium-, magnesium-, and l-lysine-enriched mineral salt added at a 75% higher level of 10.5% to produce the same sodium chloride concentration of 6%) on the cardiovascular effects produced by a low-dose combination of an angiotensin converting enzyme inhibitor ramipril (0.25 mg kg(-1) day(-1) in the food) and a calcium channel blocker felodipine (0.4 mg kg(-1) day(-1) subcutaneously via an osmotic minipump). 2 Common salt, but not the mineral salt, accelerated the development of hypertension and induced left ventricular and renal hypertrophy in SHR. Neither common salt nor mineral salt significantly affected heart rate. 3 The combination of ramipril and felodipine decreased systolic blood pressure and prevented the development of left ventricular hypertrophy effectively during the common salt diet without any significant effect on the heart rate. The cardiovascular effects of the drug combination were improved by the low sodium diet or by replacement of high common salt in the diet by mineral salt. 4 Responses of endothelium-intact mesenteric arterial rings in vitro were examined at the end of the four-week study. The combination of ramipril and felodipine markedly improved the endothelium-dependent vascular relaxation responses to acetylcholine and enhanced the endothelium-independent vascular relaxation responses to sodium nitroprusside in SHR on control and common salt diets. Replacement of common salt in the diet by mineral salt improved the endothelium-dependent vascular relaxation responses to acetylcholine. The drug combination attenuated the alpha-adrenoceptor-mediated vascular contractile responses to noradrenaline during the common salt diet. 5 Ramipril and felodipine in combination increased plasma renin activity by 1.9-3.2 fold without affecting serum aldosterone levels. 6 Our findings suggest that the cardiovascular effect of the low-dose combination of ramipril and felodipine was maintained during high salt intake. However, salt restriction or replacement of common salt in the diet by the potassium- and magnesium-enriched mineral salt improved the cardiovascular effects of the drug combination. In the face of a high intake of sodium, a part of the beneficial cardiovascular effects of the drug combination is apparently mediated by improved endothelium-dependent and endothelium-independent vascular relaxation responses and attenuated alpha-adrenoceptor-mediated vascular contractile responses.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9489606&dopt=Abstract
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