Drugs online research references
Hypertension. 1994 Apr;23(4):439-49.
Effects of converting enzyme inhibitors on angiotensin and bradykinin peptides.
Campbell DJ, Kladis A, Duncan AM.
St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
We examined the dose-related effects of angiotensin-converting enzyme inhibitors on circulating and tissue levels of angiotensin and bradykinin peptides by administering perindopril or lisinopril to rats in drinking water for 7 days. A reduction in the ratio of plasma angiotensin II (Ang II) to Ang I was seen for 0.006 mg/kg per day perindopril, with an increase in plasma renin and Ang I at 0.017 mg/kg per day. Plasma Ang II levels did not decrease until 1.4 mg/kg per day perindopril, at which dose plasma Ang I levels reached a plateau of an approximate 25-fold increase. The effects of perindopril on Ang II and Ang I levels in heart, lung, aorta, and brown adipose tissue were parallel to those observed for plasma. By contrast, renal Ang I levels did not increase, and renal Ang II levels decreased by 40% at 0.017 mg/kg per day, the same threshold seen for the increase in plasma renin. Perindopril increased circulating bradykinin-(1-9) levels approximately eightfold, with a threshold dose of 0.052 mg/kg per day, and increased bradykinin-(1-9) levels in kidney, heart, and lung in parallel with the changes observed for plasma. By contrast, aortic and brown adipose tissue bradykinin-(1-9) and bradykinin-(1-7) levels increased severalfold for perindopril doses as low as 0.006 mg/kg per day. Lisinopril also increased aortic bradykinin-(1-9) and bradykinin-(1-7) levels at doses below the threshold for the decrease in the ratio of Ang II to Ang I. These data indicate that renal Ang II levels and vascular bradykinin-(1-9) levels respond to low doses of converting enzyme inhibitor and may be important mediators of the effects of these compounds. The parallel increases in bradykinin-(1-9) and bradykinin-(1-7) levels in aorta and brown adipose tissue, at inhibitor doses below the threshold for inhibition of Ang I conversion, may result from a mechanism different from inhibition of "classic" angiotensin-converting enzyme.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8144213&dopt=Abstract
word match zestril online literature
Biochem Pharmacol. 1994 Mar 29;47(7):1121-6.
Stability and in vitro absorption of captopril, enalapril and lisinopril across the rat intestine.
Zhou XH, Li Wan Po A.
Drug Delivery Research Group, School of Pharmacy, Queen's University of Belfast, U.K.
In vitro absorption of three angiotensin converting enzyme (ACE) inhibitors, captopril, enalapril and lisinopril, and their stabilities in aqueous buffer as well as their resistance to intestinal and dermal tissue homogenates were investigated. The results demonstrate that the spontaneous oxidation of captopril, enalapril and lisinopril followed first-order degradation kinetics in McIlvaine's citrate-phosphate buffer. The degradation rates for enalapril and lisinopril were much slower than that for captopril. With the former two ACE inhibitors, the first-order rate constants of breakdown in the presence of dermal homogenate were not significantly different from the control values. Intestinal homogenate increased the decomposition of both of these inhibitors when compared to the enzyme-free control systems. On the other hand, the first-order rates of disappearance of captopril in the presence of both dermal and intestinal homogenates were lower than in the enzyme-free system. The extent of reduction was proportional to the amount of homogenate added. This suggests that tissue homogenates prevent the oxidation of captopril to its disulphide dimer. Transport experiments show that the amounts of ACE inhibitors transferred from solution on the mucosal side increased linearly with incubation time over the 2 hr of study. The rates of transfer from the mucosal side to the serosal side had the following rank order: captopril > enalapril > lisinopril roughly in the ratio 1:1.13:1.27. Addition of harmaline caused a significant reduction in the transfer rate of captopril compared to the control system, which strongly suggests that captopril is transported by a sodium-dependent carrier-mediated process across intestinal tissue.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8161340&dopt=Abstract
word match zestril online literature
Surgery. 1994 Apr;115(4):495-502.
Both lisinopril and verapamil reduced platelet-derived growth factor-A chain mRNA levels in human saphenous vein endothelial cells stimulated by thrombin.
Yamaguchi M, Gallati H, Baur W, Cruess DF, Sharefkin JB.
Department of Surgery, New England Medical Center Hospitals, Boston, Mass.
BACKGROUND. Both angiotensin-converting enzyme inhibitors and calcium channel blockers decrease postinjury intimal thickening in vivo, but their mechanisms of inhibitory action are unclear. Expression of the gene for platelet-derived growth factor (PDGF), a smooth-muscle mitogen, in endothelial cells (ECs) after vessel injury has been postulated to cause intimal thickening. In this study, we tested whether lisinopril, an angiotensin-converting enzyme inhibitor, or verapamil, a calcium channel blocker, would suppress the PDGF gene expression in stimulated human saphenous vein ECs. METHODS. Drugs were added to replicate EC cultures 30 minutes before adding 10 units/ml alpha-thrombin. Changes in PDGF-A chain mRNA levels were measured by Northern blot analysis or reverse transcription-polymerase chain reaction method. PDGF-AA homodimer in conditioned media was measured by ELISA. RESULTS. Lisinopril attenuated the induction by thrombin of PDGF-A chain mRNA levels significantly in human ECs at doses of 10(-6) mol/L and 10(-5) mol/L (p < 0.05) and appeared to decrease PDGF-AA homodimer released in conditioned medium. Verapamil also reduced thrombin induction of PDGF-A chain mRNA levels significantly at a dose of 10(-5) mol/L (p < 0.05) and appeared to reduce PDGF-AA homodimer secretion. CONCLUSIONS. These data suggest that one means by which lisinopril and verapamil both suppress intimal thickening might be inhibition of PDGF-A chain gene expression in ECs regrowing over vessel injury areas that are sites of thrombin generation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8165541&dopt=Abstract
word match zestril online literature
Herbs and Pharmaceuticals Online ||
Hair Million herbal formula for hair loss and hair growth ||
Antibiotics and prescription medications online literature ||