Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Results from animal experiments have suggested that treatment with recombinant human erythropoietin (rHuEPO) causes changes in renal hemodynamics which are detrimental to renal function. Therefore, the effects of correction of the anemia by rHuEPO on glomerular filtration rate (GFR; inulin clearance) and effective renal plasma flow (ERPF; PAH clearance) were studied in eight pre-dialysis patients. The studies were done before (Hct 0.24 +/- 0.05 liter/liter) and at 89 +/- 19 days after the start of rHuEPO therapy (Hct 0.39 +/- 0.03 liter/liter). To further evaluate the effects of ACE inhibition, 25 mg of captopril was given orally after baseline values had been obtained. Baseline GFR, renal blood flow (RBF) and filtration fraction (FF) did not change during rHuEPO therapy. At low hematocrit (Hct) captopril induced a significant increase in ERPF and RBF, and a decrease in MAP. After correction of the hematocrit the blood pressure lowering effect of captopril remained unchanged. However, captopril no longer induced changes in ERPF and RBF. We conclude that the increase in hematocrit had no adverse effects on GFR. The results suggest that changes in hematocrit may influence the effects of ACE inhibition on efferent vascular resistance. Therefore, the hematocrit should be taken into account when evaluating studies on the effects of ACE inhibition in the progression of chronic renal failure.
 ...
PMID:Evidence for renal vasodilation in pre-dialysis patients during correction of anemia by erythropoietin. 155 11

Hypertension and renal mass reduction induce glomerular hypertension (GH), hyperfiltration (HF) and renal injury. GH may contribute to allograft loss in post-transplant hypertensive patients (PT x HT). HF and GH may be evaluated by renal response to acute protein intake (API). Since ACE inhibition may prevent GH, the effects of fosinopril (Fos) were evaluated in 10 PT X HT on azathioprine and prednisone. Patients received 5 to 40 mg/day of Fos during 12 months. Baseline MAP (111.1 +/- 2.9 mm Hg) was significantly reduced by 10 to 12 mm Hg, rising to 114.7 +/- 2.7 mm Hg after Fos was administered. GFR (63.7 +/- 5.9 ml/min) decreased after 4 (48.1 +/- 4.6, P less than 0.05) and 12 months (50.7 +/- 4.6, P less than 0.05), rising to 59.4 +/- 5.6 after Fos was given. There was no GFR response to API before and after one month of Fos, however, a clear response became apparent at 4 (+ 27% P less than 0.05), and 12 months (+ 18%, P less than 0.05), disappearing after Fos discontinuation. Proteinuria (918.8 +/- 710.6 mg/d) decreased after 4 (72.3 +/- 21.6 mg/d, P less than 0.05) and 12 months, rising to 297.8 +/- 172.3 mg/day after therapy. GFR response to API in 22 controls and 17 uninephrectomized donors was 13 and 11%, respectively. Lack of response to API in PT x HT suggests HF and GH. Reduction of GFR, restoration of response to API and reduction of proteinuria, indicate that ACE inhibition with fosinopril ameliorates HF and GH. This effect may be beneficial in preventing hemodynamic-mediated allograft injury.
 ...
PMID:Fosinopril prevents hyperfiltration and decreases proteinuria in post-transplant hypertensives. 214 57

A model of congestive heart failure (CHF) was produced in rats approximately 76 days following surgical occlusion of the left coronary artery. In rats with healed myocardial infarction (MI size = 45% LV), hemodynamic variables were predictably elevated (LVEDP greater than 20 mm Hg) or depressed LV dP/dtmax (5200 mm Hg/sec). The hemodynamic response (MAP, HR, LVEDP, and dP/dtmax) to intravenous infusion of Mil (54 to 347 micrograms/kg) was measured on two occasions, separated by a 7-12 day period of oral treatment (2 mg/kg/day). Enalaprilat was tested in a similar design with the infusion phase (70 micrograms/kg, total dose) separated by oral enalapril (Enal), 1 mg/kg/day. The hemodynamic response to Mil was also examined in rats treated with the ACE inhibitor. At low doses, Mil modestly elevated HR (+17 beats/min) and dose-dependently increased (P less than 0.05) LV contractility by approximately 25%. Higher doses of Mil reduced preload (LVEDP) and afterload (MAP). Oral Mil produced little hemodynamic improvement except modest elevation (+9%) in LV contractility. There was no evidence of tachyphylaxis to i.v. Mil. In contrast, enalaprilat reduced MAP and preload without altering HR or contractility, effects observed after oral treatment. In the presence of the ACE inhibitor, Mil's hemodynamic actions were not enhanced. These experiments demonstrate that ACE inhibition improves ventricular performance by reducing preload and afterload. In this model, Mil improves performance by a direct inotropic mechanism as well as a reduction in afterload.
 ...
PMID:Acute and subacute hemodynamic effects of enalaprilat, milrinone and combination therapy in rats with chronic left ventricular dysfunction. 303 90

Since dietary salt loading enhances nitric oxide (NO) generation in the kidney, we investigated the hypothesis that changes in salt intake have specific effects on vascular resistance in the kidney mediated by the L-arginine-NO pathway. We contrasted changes in renal and hindquarter vascular resistances (RVR and HQVR) in anesthetized rats during intravenous infusions of graded doses of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Groups (N = 8 to 10) of rats were maintained on a high salt (HS) or low salt (LS) diet for two weeks. Compared to those on LS, rats on HS had a greater increase in mean arterial pressure (delta MAP; +32 +/- 4 vs. +22 +/- 3%; P = 0.05) and RVR (+160 +/- 17 vs. +83 +/- 10%; P < 0.005) and a greater fall in renal blood flow (delta RBF; -47 +/- 3 vs. -32 +/- 4%; P < 0.01); changes in HQVR were similar in the two groups. The enhanced RVR response to L-NAME in HS rats could not be ascribed to the higher renal perfusion pressure (RPP) since it persisted in rats whose RPP was controlled by adjustment of a suprarenal aortic clamp. Changes in RVR with an NO donor (SIN-1) were similar in HS and LS rats. L-NAME reduced plasma renin activity in both HS and LS rats. After inhibition of ACE with captopril, or of angiotensin II type I (AT1) receptor with losartan, the increase in RVR with L-NAME remained greater in HS than LS rats.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Renal vasoconstriction during inhibition of NO synthase: effects of dietary salt. 752 72

ACE-inhibitors are known to have special renal effects, i.e. they increase ERPF, decrease the filtration fraction and lower proteinuria. These effects can be due to a decrease in angiotensin II (AII) levels as well as an increase in bradykinin. New and more specific AII-receptor antagonists may help to distinguish between effects exerted by angiotensin II and those exerted by bradykinin. We investigated the effects of losartan in 9 patients with essential hypertension (sitting mean diastolic blood pressure 95-120 mmHg). Renal hemodynamics were measured by continuous inulin-and PAH-clearance (GFR and RPF) after stopping antihypertensive therapy for 1 week, followed by a 2-week placebo period and after a 4-week treatment phase with losartan (50 mg/die) followed by a therapy with an ACE-inhibitor (ramipril 5mg/die). Additionally, urine albumin excretion (UAE) was measured. Treatment of patients with essential hypertension with losartan resulted in a significant decrease of MAP after three weeks of treatment (121 +/- 8 mmHg under placebo and 114 +/- 10 mmHg under losartan; * = p < 0.05). MAP after four weeks of losartan treatment was 115 +/- 11 mmHg. Regarding changes in renal hemodynamics we could not demonstrate a significant change for neither losartan nor the ACE-inhibitor. Urine albumin excretion was reduced by both treatment regimens in correlation to the magnitude of blood pressure reduction. Our data indicate that losartan induced a significant reduction in MAP in patients with essential arterial hypertension with only moderate effects on renal hemodynamics.
 ...
PMID:Renal hemodynamics in essential hypertensives treated with losartan. 778 Dec 6

The progression of diabetic nephropathy can be positively influenced by maintaining a low blood pressure level. This has been shown in studies with conventional antihypertensive treatment as well as with ACE inhibitors. Whether the latter group of drugs is more effective remains to be proven and was the aim of our study. In a prospective randomized study we compared the effects of ACE inhibition and beta-blockade on retarding progression of renal function in IDDM patients with an early stage of overt diabetic nephropathy. Twenty-nine patients were studied for 2 years, 15 were randomized for treatment with captopril and 14 for atenolol. Every 6 weeks blood pressure and urinary albumin and total protein excretion were measured. GFR was measured every 6 months as 51Cr-EDTA clearance. Baseline values for blood pressure, renal function and albuminuria were identical in the two groups. The effect of both drugs on blood pressure was not significantly different. In the captopril-treated patients MAP before and after 2 years was 110 +/- 3 (SEM) and 100 +/- 2 mm Hg, respectively and in the atenolol-treated patients 105 +/- 2 vs 101 +/- 2 mm Hg. Both drugs reduced albuminuria and total proteinuria to the same extent. With captopril albuminuria decreased from 1549 (989-2399) to 851 (537-1380) mg/24 h and proteinuria from 2.5 (1.6-3.8) to 1.2 (0.8-1.8) g/24 h. With atenolol albuminuria decreased from 933 (603-1445) to 676 (437-1047) mg/24 h and proteinuria from 1.5 (1.0-2.4) to 0.9 (0.6-1.5) g/24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Captopril and atenolol are equally effective in retarding progression of diabetic nephropathy. Results of a 2-year prospective, randomized study. 774 19

The effect of 24-hour unilateral ureteral obstruction (UUO) on the expression and regulation of the renin-angiotensin system (RAS) in rats and of pretreatment with lisinopril (5 mg/kg/day) or the AT1-R inhibitor, losartan, (10 mg/kg/day) on renal hemodynamics was evaluated. Both drugs improved the post-obstructed kidney (POK) renal hemodynamics, lowered MAP, and normalized eicosanoid excretion by the POK. Cortex and medulla POK:CK ratio of relative density R mRNA was approximately 3.5 for both. Sham, POK, and CK showed renin immunoreactivity and R mRNA exclusively in juxtaglomerular position. In addition, in POK renin was expressed in mesangial cells, along greater lengths of afferent arterioles and in dilated distal tubules and loops of Henle. In situ hybridization revealed that approximately 20% more glomeruli in POK than CK overexpressed R mRNA. Blood vessels of POK consistently showed greater ACE and Ao mRNA expression than CK. Overexpression of the genes coding for members of the RAS is possibly responsible for local Ang II production which, in view of the response to CEI and AT1-R inhibitors, is at least partly responsible for the severe hemodynamic changes in UUO.
 ...
PMID:Regulation of renin-angiotensin system in unilateral ureteral obstruction. 839 17

Several observations question the role of blood pressure and renal hemodynamic changes in the long-term antiproteinuric effect of ACE inhibition. To differentiate blood pressure and renal effects in the initial antiproteinuric response, the placebo-controlled acute effects of the ACE inhibitor enalaprilat (10 mg i.v.) on blood pressure, renal hemodynamics, and proteinuria were compared with those of nitroprusside in nine patient with non-diabetic proteinuria. In addition, we studied whether an exogenous angiotensin II infusion reverse the initial enalaprilat-induced antiproteinuric response. Enalaprilat and nitroprusside reduced MAP by -11.3 +/- 2.4% and -14.1 +/- 2.3%, respectively, whereas only enalaprilat showed renal hemodynamic effects, reflected by an increase in ERPF of 18.4 +/- 5.4% and a decrease in FF of -17.1 +/- 2.6%. Despite the contrasting renal hemodynamic profiles, enalaprilat (-10.6 +/- 4.8%) and nitroprusside (-12.8 +/- 5.1% equally decreased proteinuria. Exogenous infusion of angiotensin II completely reversed the blood pressure reduction and renal efferent vasodilatation induced by enalaprilat. proteinuria also increased by 13.1 +/- 7.8% to placebo level, albeit statistically non-significant. We conclude that the initial antiproteinuric effect of ACE inhibition appears to be mediated by blood pressure reduction and does not require its specific renal hemodynamic effect. Further studies should clarify whether the renal efferent vasodilatation during ACE inhibition is required to gradually induce renal structural changes that prevent the abundant passage of proteins.
 ...
PMID:Blood pressure reduction initiates the antiproteinuric effect of ACE inhibition. 877 Sep 65

Previous reports have suggested that NO is an important mediator of the antihypertensive effects of renin-angiotensin system (RAS) inhibition. We examined the effects of the NO synthase inhibitor L-NNA on the hypotensive effects of captopril, the Ang II antagonist EXP 3174, or the renin inhibitor terlakiren. In sodium-depleted guinea pigs (GPs), L-NNA (3 mg/kg) increased MAP by 15-21% for at least 5 hours. L-NNA partially blocked the hypotensive effects of captopril (1 mg/kg, iv), but not those of EXP 3174 (1 mg/kg, iv) or terlakiren (3 mg/kg). In sodium-depleted rats, 10 mg/kg L-NNA (iv) increased MAP by 16-22%, and partially or fully blocked the hypotensive effect of EXP 3174 (1 mg/kg, iv) or captopril (3 mg/kg, iv), respectively. Thus, in contrast to the rat, NO in GPs appears to participate only in the hypotensive action of ACE inhibition and does not appear to be strongly involved in the hypotensive action of AII antagonism or renin inhibition. The involvement of NO in the hypotensive effects of RAS antagonists other than ACE inhibitors may be species-dependent.
 ...
PMID:Role of nitric oxide in responses to renin-angiotensin system inhibition in sodium-depleted guinea pig and rat. 953 11

In 34 out-patients with essential hypertension, the antihypertensive effect and the trough-to-peak ratios of once-daily enalapril or lisinopril were compared by ambulatory blood pressure monitoring (ABPM) according to a crossover design. The drug dose was titrated and a thiazide diuretic was added if necessary to attain a target office BP of less than 140/90 mm Hg. Both drugs significantly lowered BP but the effect of lisinopril was greater (P < 0.009): day- and night-time mean BP fell from 152/98 and 135/84 mm Hg, respectively to 133/85 and 118/74 mm Hg with enalapril and to 129/83 and 116/70 mm Hg with lisinopril. BP goal was reached with an average dose of 18 mg enalapril with 8 mg hydrochlorothiazide and with 17 mg lisinopril combined with 6 mg diuretic. Trough:peak ratio values, which were calculated after Fourier analysis of ABPM data in individual patients, were independent of drug dose. The combination with the diuretic resulted in slightly higher trough:peak ratios than with ACE inhibitor monotherapy, but the difference was not significant. The median trough:peak ratio in patients when using enalapril-based therapy was 0.48 and, when taking lisinopril-based treatment, it was 0.65 (n = 28, P < 0.005). A significant correlation was found between trough:peak ratio and changes in daytime mean arterial pressure (MAP; Spearman r= 0.43) and night-time MAP (r= 0.66). When 24-h ABPM was performed starting 24 h after last drug intake, both ACE inhibitors still had a significant antihypertensive effect (P < 0.001), which was similar for both drugs. Eleven patients reported minor side effects. Four patients stopped ACE-inhibitor treatment because of cough. The data show that lisinopril has a longer duration of action than enalapril.
 ...
PMID:Lisinopril versus enalapril: evaluation of trough:peak ratio by ambulatory blood pressure monitoring. 1040 91


1 2 3 Next >>