Year-long antihypertensive therapy with candesartan completely prevents development of cardiovascular organ injuries in spontaneously hypertensive rats.

Most previous studies have examined the effects of antihypertensive drugs in hypertensive animals for only a few months, and little information has been provided as to the protective effects of lifetime antihypertensive medication against cardiovascular organ injury. In this study, spontaneously hypertensive rats (SHR) were treated for 1 year with an angiotensin-II receptor antagonist (ARB) and the development of hypertensive organ injury was evaluated. Male 15-week-old SHR (n = 9) were given 25 mg/L candesartan (CS) in their drinking water for 1 year.

Valsartan improves L-NAME-exacerbated cardiac fibrosis with TGF-ß inhibition and apoptosis induction in spontaneously hypertensive rats.

This study was designed to investigate whether chronic angiotensin II type 1 receptor blockade inhibits ventricular interstitial fibrosis with the induction of programmed cell death (apoptosis) in prolonged nitric oxide synthase (NOS) inhibition using N(G)-nitro-l-arginine methyl ester (L-NAME) in spontaneously hypertensive rats (SHR). Four groups of 20-week-old male SHR were studied for 3 weeks: the control group; the L-NAME group given 80 mg/L L-NAME in drinking water; and the groups given 1 or 30 mg/(kg day) of valsartan, respectively, with L-NAME. The L-NAME group showed marked cardiac tissue injuries with elevated blood pressure such as interstitial fibrosis, intimal thickening of small arteries, and myocardial necrosis.

Combination therapy with telmisartan and spironolactone alleviates L-NAME exacerbated nephrosclerosis with an increase in PPAR-gamma and decrease in TGF-beta(1).

To investigate whether the receptor blockades of angiotensin II type 1 and aldosterone receptors can prevent renal tissue injury in relation to the renal tissue mRNA levels of peroxisome proliferation-activated receptors-gamma (PPAR-gamma) and transforming growth factor-beta (1) (TGF-beta(1)) in spontaneously hypertensive rats (SHR) given N(G)-nitro-L-arginine methyl ester (L-NAME), which is considered a model of malignant hypertension. This study was performed in 5 groups of 17-week-old male SHR treated for 3 weeks as follows: group 1, control; group 2, L-NAME (50 mg/L in drinking); group 3, L-NAME plus aldosterone antagonist, spironolactone (SPRL, 100 mg/kg/day); group 4, L-NAME plus angiotensin II type 1 receptor blocker, telmisartan (TELM, 3 mg/kg/day); group 5, L-NAME plus combination therapy (COMB) with low-dose TELM (1 mg/kg/day) and SPRL (100 mg/kg/day). Urinary protein excretion and the glomerular injury score were significantly reduced in the SPRL, TELM, and COMB groups as compared with the L-NAME group, while significant blood pressure reduction was observed only in the TELM group.

Efonidipine reduces proteinuria and plasma aldosterone in patients with chronic glomerulonephritis.

Efonidipine, a dihydropirydine calcium channel blocker, has been shown to dilate the efferent glomerular arterioles as effectively as the afferent arterioles. The present study compared the chronic effects of efonidipine and amlodipine on proteinuria in patients with chronic glomerulonephritis. The study subjects were 21 chronic glomerulonephritis patients presenting with spot proteinuria greater than 30 mg/dL and serum creatinine concentrations of View Article and Find Full Text PDF

Benazepril slows progression of renal dysfunction in patients with non-diabetic renal disease.

Aim: The present study examined the effects of benazepril, an angiotensin-converting enzyme inhibitor, on the progression of renal insufficiency in patients with non-diabetic renal disease.

Methods: Fifteen patients with non-diabetic renal disease whose serum creatinine (Cr) ranged from 1.5 to 3.

Inhibition of Rho-kinase attenuates nephrosclerosis and improves survival in salt-loaded spontaneously hypertensive stroke-prone rats.

Objectives: We examined whether the Rho/Rho-kinase pathway is involved in the pathogenesis of nephrosclerosis in severely hypertensive rats and assessed the effects of long-term treatment with a Rho-kinase inhibitor, fasudil, on kidney function, histological findings, gene expressions, and survival. We also attempted to elucidate the mechanisms involved.

Methods: We studied the following four groups: control Wistar-Kyoto rats (WKY), untreated salt-loaded spontaneously hypertensive stroke-prone rats (SHR-SP), low-dose fasudil (15 mg/kg per day)-treated SHR-SP, and high-dose fasudil (30 mg/kg per day)-treated SHR-SP.

Cardiorenal protective effects of year-long antihypertensive therapy with an angiotensin-converting enzyme inhibitor or a calcium channel blocker in spontaneously hypertensive rats.

Background: The objective of this study was to evaluate the effect of year-long antihypertensive therapy with a calcium channel blocker and an angiotensin-converting enzyme (ACE) inhibitor on cardiac and renal injury.

Methods: Male 15-week-old spontaneously hypertensive rats (SHR) were given either a normal diet and normal drinking water (n = 10), a diet containing 0.05% nitrendipine (n = 10), or drinking water containing 50 mg/L of quinapril (n = 10).

Long-term administration of rho-kinase inhibitor ameliorates renal damage in malignant hypertensive rats.

We have shown recently that fasudil, a Rho-kinase inhibitor, has renoprotective effects in salt-sensitive hypertensive rats. We hypothesized that activation of Rho-kinase is involved in the pathogenesis of glomerulosclerosis in malignant hypertensive rats. To test this hypothesis, we studied the following 4 groups: control Wistar-Kyoto rats, untreated deoxycorticosterone-acetate salt spontaneously hypertensive rats (DOCA-SHR), low-dose fasudil-treated DOCA-SHR, and high-dose fasudil-treated DOCA-SHR.

Pathophysiologic and therapeutic implications of adrenomedullin in cardiovascular disorders.

Adrenomedullin (AM) is a vasodilator peptide that originally isolated from pheochromocytoma tissue. However, the mRNA is expressed in the normal adrenal gland, heart, kidney and blood vessels. The human AM gene is located in the short arm of chromosome 11 and is composed of 4 exons.

Effects of valsartan on the progression of chronic renal insufficiency in patients with nondiabetic renal diseases.

The present study tested the effects of valsartan, an angiotensin II receptor blocker, on the progression of renal insufficiency in patients with nondiabetic renal diseases. The study subjects were 22 patients with nondiabetic renal diseases whose serum creatinine (Cr) ranged from 1.5 to 3.

Renoprotective effect of long-term combined treatment with adrenomedullin and omapatrilat in hypertensive rats.

Background: Previous studies demonstrated that adrenomedullin (AM) is metabolized by neutral endopeptidases and that the renal effect of AM is augmented by the inhibition of neutral endopeptidases. We have recently shown that the long-term administration of AM has renoprotective effects.

Object: This study assessed the chronic renoprotective effects of AM combined with a vasopeptidase inhibitor in hypertensive rats and attempted to elucidate the mechanism involved.

Protective effects of an angiotensin II receptor blocker and a long-acting calcium channel blocker against cardiovascular organ injuries in hypertensive patients.

The purpose of this study is to compare the long-term effects of an angiotensin II receptor blocker (ARB) and a long-acting calcium channel blocker (CCB) on left ventricular geometry, hypertensive renal injury and a circulating marker of collagen synthesis in hypertensive patients. Patients with essential hypertension (24 men and 19 women; age, 37-79 years) were treated with a long-acting CCB, amlodipine (AML; 2.5-7.

[Effects of intravascular contrast media on urinary excretion of liver fatty acid-binding protein].

Proximal tubules of the kidney produce liver fatty acid-binding protein (L-FABP) and the level of messenger RNA is increased by physical and chemical stimuli. In this study, changes in urinary excretion of L-FABP were examined in 18 patients without renal dysfunction and who had undergone angiography using iodinated contrast media. On the day following angiography, the urinary excretion of L-FABP was markedly increased by 578 % (p<0.

Superiority of combination of thiazide with angiotensin-converting enzyme inhibitor or AT1-receptor blocker over thiazide alone on renoprotection in L-NAME/SHR.

The renal and glomerular dynamic effects of combining thiazide and angiotensin antagonists have not been reported. The present study was designed to examine the effects of hydrochlorothiazide (HCTZ) alone or in combination with an angiotensin-converting enzyme inhibitor or ANG II type 1-receptor blocker on renal hemodynamics, glomerular dynamics, renal function, and renal histopathology in the N(omega)-nitro-l-arginine methyl ester-treated spontaneously hypertensive rat (l-NAME/SHR) model. HCTZ (80 mg x kg(-1) x day(-1)) alone or in combination with enalapril (30 mg x kg(-1) x day(-1)) or losartan (30 mg x kg(-1) x day(-1)) or enalapril (15 mg.

Urinary excretion of liver fatty acid-binding protein in health-check participants.

Background: Messenger RNA of liver fatty acid-binding protein (L-FABP) is expressed in proximal tubules of the kidney, and a certain amount is excreted into urine. We analyzed factors relating to the urinary L-FABP excretion in health-check participants.

Methods: We measured L-FABP in the first morning urine by ELISA in 715 men and 193 women 30-79 years of age who entered a 2-day hospitalized health checkup program.

[Angiotensin type 1 receptor blocker reduced proteinuria in patients of focal glomerular sclerosis].

We report three cases of focal glomerular sclerosis (FGS) with proteinuria that improved with the administration of angiotensin type 1 receptor blocker (ARB, losartan or valsartan). These three patients were a 41-year-old male (case 1), a 22-year-old male (case 2) and a 47-year-old male (case 3), who showed proteinuria, renal dysfunction, and hyperlipidemia. In case 1, proteinuria and renal dysfunction were improved by losartan administration and low protein diet therapy.

Increased cardiovascular risk in long-term hemodialysis patients carrying deletion allele of ACE gene polymorphism.

Background: Controversy continues about the relation of insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene to the genetic predisposition to develop such cardiovascular diseases as myocardial infarction, stroke, and other arteriosclerotic disorders.

Methods: To examine the relation of ACE gene polymorphism to risk for developing cardiovascular diseases in long-term hemodialysis patients, we followed up 534 patients on long-term hemodialysis therapy for 3 years after determining ACE genotype.

Results: Numbers of patients with the II, ID, and DD genotypes were 208, 245, and 81, and frequencies of the I and D alleles were 0.

Fasudil, a Rho-kinase inhibitor, attenuates glomerulosclerosis in Dahl salt-sensitive rats.

Objective: The present study was designed to clarify whether the Rho-Rho-kinase pathway is involved in the process of hypertensive glomerulosclerosis and to assess the therapeutic effect of fasudil, a specific Rho-kinase inhibitor.

Method And Results: Dahl salt-sensitive rats (DS) and Dahl salt-resistant rats (DR) were fed a high-salt diet at 6 weeks of age. Fasudil (30 mg/kg per day) was administered for 7 weeks to DS starting at the age of 11 weeks.

Imidapril improves L-NAME-exacerbated nephrosclerosis with TGF-beta 1 inhibition in spontaneously hypertensive rats.

Objective: This study was designed to investigate whether chronic angiotensin-converting enzyme (ACE) inhibition prevents hypertensive glomerular injury and inhibits increases in the mRNA levels and immunohistological expression of the apoptosis inducer caspase-3, and transforming growth factor (TGF)-beta 1 during prolonged nitric oxide synthase (NOS) inhibition with N-nitro-L-arginine methyl ester (L-NAME) in spontaneously hypertensive rats (SHR).

Methods And Results: For 3 weeks, we studied three groups of 20-week-old male SHR: a control group, a l-NAME group, and a group treated with L-NAME and the ACE inhibitor imidapril. L-NAME rats developed severe hypertensive nephrosclerosis with significantly elevated blood pressure, markedly increased urinary protein excretion and serum creatinine levels, and more severe glomerulosclerosis and tubulo-interstitial changes.

Aldosterone antagonism ameliorates proteinuria and nephrosclerosis independent of glomerular dynamics in L-NAME/SHR model.

Background: The renin-angiotensin-aldosterone system participates importantly in the progression of hypertensive renal disease. Angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists have been demonstrated to afford renoprotection in L-NAME-exacerbated nephrosclerosis in SHR rats. This study was designed to examine the effects of the aldosterone antagonist eplerenone on systemic and renal hemodynamics, glomerular dynamics, renal function and histopathology in L-NAME/SHR, and determine whether aldosterone antagonism would enhance the effectiveness of ACE inhibition.

Renoprotective effects of omapatrilat are mediated partially by bradykinin.

Aim: To investigate the effects of omapatrilat on systemic and renal hemodynamics, glomerular dynamics, renal function, and histopathological changes as well as the participation of the bradykinin B2 receptor in WKY, SHR, and L-NAME/SHR rats.

Methods: Eight groups of 17-week-old rats were examined using renal micropuncture techniques and histopathological analyses after 3 weeks of treatment: group 1, WKY control; group 2, WKY+omapatrilat (40 mg/kg/day); group 3, SHR control; group 4, SHR+omapatrilat; group 5, SHR+L-NAME (50 mg/l); group 6, SHR+L-NAME+omapatrilat; group 7, SHR+L-NAME for 3 weeks followed by omapatrilat for a subsequent 3 weeks, and group 8, SHR+L-NAME+omapatrilat+bradykinin antagonist icatibant (500 microg/kg/day).

Results: In WKY and SHR, omapatrilat significantly reduced the mean arterial pressure, increased effective renal blood flow and single nephron plasma flow associated with reduced glomerular arteriolar resistances.

Microsatellite DNA polymorphism of human adrenomedullin gene in type 2 diabetic patients with renal failure.

Background: Adrenomedullin (AM) is a hypotensive peptide widely produced in the cardiovascular organs and tissues such as the heart, kidney, and the vascular cells. We have previously cloned and sequenced the genomic DNA encoding human AM gene, and determined that the gene is located in the short arm of chromosome 11. The 3'-end of the gene is flanked by the microsatellite marker of cytosine adenine (CA) repeats.

Variations of human adrenomedullin gene and its relation to cardiovascular diseases.

The studies concerning the structure and variations of the human adrenomedullin (AM) gene are reviewed, and their relations to the gene function and genetic predisposition to cardiovascular diseases are discussed. The genomic human AM gene is composed of four exons, and the whole nucleotide sequence corresponding to mature AM resides in the fourth exon. In chromosomal sublocalization, the AM gene is located in the distal portion of the short arm of chromosome 11 (11p15.

Relations of plasma high-sensitivity C-reactive protein to traditional cardiovascular risk factors.

Variations of circulating C-reactive protein (CRP) levels are supposed to reflect chronic inflammatory process of the cardiovascular system. In particular, it has been reported that high-sensitivity CRP (hsCRP) is a promising marker of coronary heart disease. In the present study, we assessed the relationship between hsCRP and classic cardiovascular risk factors, such as age, blood pressure, smoking habit and serum lipids.