Comparison of Inhibitory Effects between Enalapril and Losartan on Adrenal Catecholamine Secretion

BACKGROUND: The present study was attempted to compare enalapril, an angiotensin-converting enzyme inhibitor with losartan an angiotensin II (Ang II) receptor blocker in the inhibitory effects on the secretion of catecholamines (CA) from the perfused model of the rat adrenal gland. METHODS: The adrenal gland was isolated and perfused with Krebs-bicarbonate. CA was measured directly by using the fluorospectrophotometer. RESULTS: Both enalapril and losartan during perfusion into an adrenal vein for 90 minutes inhibited the CA release evoked by acetylcholine (ACh), 1.1-dimethyl-4-phenyl piperazinium (DMPP, a selective Nn agonist), high K+ (a direct membrane-depolarizer), 3-(m-chloro-phenyl-carbamoyl-oxy-2-butynyl-trimethyl ammonium (McN-A-343, a selective M1 agonist), and Ang II in a time-dependent manner. Also, in the presence of enalapril or losartan, the CA release evoked by veratridine (an activator of voltage-dependent Na+ channels), 6-dimethyl-3-nitro-4-(2-trifluoromethyl-phenyl)-pyridine-5-carboxylate (BAY-K-8644, an L-type Ca2+ channel activator), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor) were significantly reduced. Based on the same concentration of enalapril and losartan, for the CA release evoked by ACh, high K+, DMPP, McN-A-343, Ang II, veratridine, BAY-K-8644, and cyclopiazonic acid, the following rank order of inhibitory potency was obtained: losartan > enalapril. In the simultaneous presence of enalapril and losartan, ACh-evoked CA secretion was more strongly inhibited compared with that of enalapril- or losartan-treated alone. CONCLUSIONS: Collectively, these results demonstrate that both enalapril and losartan inhibit the CA secretion evoked by activation of both cholinergic and Ang II type-1 receptors stimulation in the perfused rat adrenal medulla. When these two drugs were used in combination, their effects were enhanced, which may also be of clinical benefit. Based on concentration used in this study, the inhibitory effect of losartan on the CA secretion seems to be more potent than that of enalapril.

Selection of Antihypertensive Drugs in Hypertensive Patients with Diabetes Mellitus: In Pohang-Gyeongju Primary Care Research Network

BACKGROUND: Angiotensin converting enzyme inhibitor or Angiotensin II type 1 receptor blocker is usually recommended for hypertensive patients with diabetes mellitus. No reports have been made on antihypertensive agents prescribed for these patients in private practice. METHODS: During a one month period of December 2004, 169 hypertensive patients with diabetes mellitus on their prescribed antihypertensive agents by ten family physicians were analyzed. The influencing factors for such prescriptions were analyzed by directly visiting each physicians who prescribed them. RESULTS: A total of 21 antihypertensive agents were prescribed by these family physicians. Single calcium channel blocker therapy was the most common with 55 cases (32.5%), followed by 20 cases (11.8%) of single angiotensin converting enzyme inhibitor therapy and 16 cases of single therapy of Angiotensin II type 1 receptor blocker. The low frequency of prescribing the Angiotensin II type 1 receptor blocker was due to insufficient effect (7), lack of information (5), resistance from the patients from changing the medications (4) and expensive costs (4). CONCLUSION: In prescribing antihypertensive agents for patients with diabetes mellitus, angiotensin converting enzyme inhibitor or Angiotensin II type 1 receptor blocker were chosen less. In order to decrease the incidence of complications in these patients, such agents should be prescribed more.

Changes of ZO-1 Expression in Diabetic Rat Glomeruli and Cultured Mouse Podocyte Under High Glucose Conditions and the Effect of Angiotensin II Type 1 Receptor Blocker / 대한신장학회잡지

BACKGROUND: Diabetic nephropathy (DN) is clinically characterized by persistent proteinuria. The underlying pathologic changes responsible for the nephropathy are the loss of size selective and/or charge selective properties of the glomerular filtration barrier. Size selectivity is maintained primarily by the slit diaphragm and ZO-1 is one of the basic components of it. However, the precise role of the ZO-1 in the pathogenesis of the glomerular diseases is not fully understood. We investigated the changes of ZO-1 expression in diabetic glomeruli in vivo, and by high glucose in cultured podocyte in vitro. We also evaluated the effect of angiotensin II type 1 receptor blocker (ARB) on the ZO-1 changes induced by diabetes or high glucose. METHODS: To determine the effect of ARB on podocytes ZO-1 protein and mRNA expression, immortalized mouse podocytes were incubated with RPMI medium containing normal glucose (NG, 5.6 mM) or high glucose (HG, 30 mM) with or without ARB (10-6 M, L-158, 809). For animal studies, rats were injected with diluent (Control, C, n=18) or streptozotocin. The latter were left untreated (DM, n=18) or treated with 1 mg/kg/day ARB (DM+ARB, n=18). Six rats from each group were sacrificed monthly, and Western blot and RT?PCR were performed for ZO-1 with sieved glomeruli. Renal sections were stained for ZO-1 by immunohistochemistry. RESULTS: The ZO-1 mRNA and protein expressions in podocytes exposed to HG conditions were significantly higher than those in podocytes exposed to NG media (p<0.05). ARB treatment inhibited the HG induced increase in ZO-1 mRNA and protein expression by 73% and 64%, respectively (p<0.05). Compared to the C rats (19.8+/-3.2 mg/day), 24 hour urinary protein excretion at 3 month was significantly higher in the DM rats (90.6+/-11.3 mg/day, p< 0.05), and ARB treatment partly reversed the increase in proteinuria in DM rats (51.6+/-6.6 mg/day, p<0.05). Glomerular ZO-1 mRNA and protein expressions were also significantly increased in DM than corresponding C at all duration (p<0.05). ARB treatment for 3 months in DM rats inhibited the increase in ZO-1 mRNA and protein expression by 57.5% and 70.6%, respectively (p<0.05). ARB treatment for 3 months significantly ameliorated increased glomerular ZO-1 expression in DM rats as assessed by immunohistochemistry. CONCLUSION: In conclusion, ZO-1 mRNA and protein expressions were increased in podocytes exposed to HG and in DM glomeruli, and this increment in ZO-1 expression was ameliorated with ARB. Taken together, these data suggest that change of ZO-1 expression in podocytes is implicated in the early changes of diabetic nephropathy and may contribute to the development of proteinuria.