cardiovascular-agents and Hypertension--Renal

Renal artery stenosis (RAS) is usually caused by atherosclerosis or fibromuscular dysplasia. RAS leads to activation of the renin-angiotensin-aldosterone system and may result in hypertension, ischemic nephropathy, left ventricular hypertrophy and congestive heart failure. Management options include medical therapy and revascularization procedures. Recent studies have shown angiotensin receptor blockers (ARB) and angiotensin converting enzyme inhibitors (ACE-I) to be highly effective in treating the hypertension associated with RAS and in reducing cardiovascular events; however, they do not correct the underlying RAS and loss of renal mass may continue. Renal artery angioplasty was first performed by Gruntzig in 1978. The routine use of stents has increased technical success rates compared with angioplasty, and surgery is now only rarely performed. Although numerous case series claimed benefit in terms of blood pressure control, no adequately powered randomized, controlled, prospective study of renal artery interventions has reported their effect on cardiovascular morbidity or mortality. The CORAL trial, an ongoing study of renal artery stent placement and optimal medical therapy (OMT) funded by the National Institutes of Health, is the first study to attempt to do so. Until the CORAL trial results are in, physicians will continue to be faced with difficult choices when determining the optimal management for RAS patients and deciding which, if any, patients should be offered revascularization.

Topics: Angioplasty, Balloon; Atherosclerosis; Blood Pressure; Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Evidence-Based Medicine; Humans; Hypertension, Renal; Kidney Function Tests; Patient Selection; Radiography; Renal Artery Obstruction; Risk Assessment; Risk Factors; Stents; Treatment Outcome

Cardiovascular diseases remain the leading cause of death in ESRF patients. Coronary risk factors such as hypertension and lipid abnormalities are prevalent in the dialysis population and may be difficult to control. Special factors contributing to the imbalance between myocardial oxygen supply and demand include anemia, arteriovenous fistula, and the hemodialysis procedure itself. LVH and left ventricular dilation frequently result in symptomatic CHF. Atrial and ventricular arrhythmias are common; pericarditis may also occur. Control of the extracellular fluid volume through ultrafiltration with dialysis and the dietary avoidance of salt and water is critical to controlling hypertension in the dialysis population. The potential for drug side effects and the altered pharmacokinetics of medications in renal failure patients should be considered when prescribing cardiovascular drugs.

Topics: Cardiovascular Agents; Heart Diseases; Humans; Hypertension, Renal; Hypotension; Kidney Failure, Chronic; Renal Dialysis; Risk Factors

Ginkgo biloba leaves extract has been widely used worldwide to protect against oxidative stress-induced cell damage and improves blood circulation.. The potential protective role of the standardized leaf extract of Ginkgo biloba (EGb761) on hypertension-induced renal injury was investigated in rats. Hypertension was induced in rats by L-NAME.. Repeated treatment with EGb761 produced progressive reductions in the systolic, diastolic and mean arterial blood pressure. Also, EGb761 increased the progressive reductions in blood pressure induced by losartan. Hypertension-induced marked elevation of renal malondialdehyde (MDA) and nitrite levels and reduction of reduced glutathione (GSH) level were inhibited by EGb761. In addition, hypertension-induced increases in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β)) levels in renal tissues were inhibited by EGb761. Also, treatment with EGb761 inhibited hypertension-induced decrease in endothelial nitric oxide synthase (eNOS) protein expression and increase in the protein expressions of inducible NO synthase (iNOS), TNF-α, IL-6 and IL-1B in the kidney tissues. EGb761 enhanced losartan effects on renal tissues oxidative stress, nitrite, and inflammatory markers levels and on protein expressions of eNOS, iNOS, TNF-α, IL-6 and IL-1B. effects.. These results indicate that EGb761 has the ability to protect against hypertension-induced renal injury.

Topics: Animals; Antihypertensive Agents; Arterial Pressure; Cardiovascular Agents; Ginkgo biloba; Glutathione; Hypertension; Hypertension, Renal; Interleukin-1beta; Interleukin-6; Kidney; Kidney Diseases; Losartan; Male; Malondialdehyde; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Oxidative Stress; Plant Extracts; Rats; Tumor Necrosis Factor-alpha

trans-Resveratrol (resveratrol) has been shown to have beneficial effects on the cardiovascular system in a number of studies. It is, however, unclear whether this naturally occurring compound can protect against cardiac hypertrophy. The aim of the present study was to investigate the effects of resveratrol on cardiac hypertrophy in vivo and the potential underlying mechanisms involving endothelin (ET), angiotensin (Ang) II and nitric oxide (NO) in partially nephrectomized rats. Animal models bearing cardiac hypertrophy were replicated in male Sprague-Dawley rats following partial nephrectomy (PNX). Resveratrol (10 or 50 mg/kg) was administered to rats by gavage for 4 weeks. Simultaneous PNX and sham operation controls were simultaneously established in the present study. The systolic blood pressure (SBP) of rats was measured at baseline and, along with heart weight, after 4 weeks treatment. Serum ET-1, AngII and NO concentrations were determined. In the present study, it was shown that, compared with rats in the sham-operated group, rats in the PNX group had significantly higher SBP (154.1 +/- 22.7 mmHg), heart weight (1.69 +/- 0.24 g) and serum ET-1 (125.70 +/- 26.27 pg/mL) and AngII serum concentrations (743.63 +/- 86.50 pg/mL), whereas serum NO concentrations were lower (21.1 +/- 6.9 micromol/L; all P < 0.05). These values in the sham control group were 114 +/- 10 mmHg, 1.28 +/- 0.13 g, 52.44 +/- 21.85 pg/mL, 528.7 +/- 158.5 pg/mL and 53.21 +/- 23.87 micromol/L, respectively. After 4 weeks treatment with 50 mg/kg resveratrol, SBP, heart weight and ET-1 and AngII concentrations had decreased to 135.4 +/- 15.8 mmHg, 1.39 +/- 0.15 g, 97.11 +/- 26.74 pg/mL and 629.64 +/- 116.18 pg/mL, respectively. However, the serum NO concentration had increased to 40.1 +/- 14.6 micromol/L. These values were significantly different from those obtained for the PNX group. In conclusion, trans-resveratrol appears to be able to protect against the increase in SBP and subsequent cardiac hypertrophy in vivo and the mechanisms responsible may involve, at least in part, modulation of NO, AngII and ET-1 production.

Topics: Angiotensin II; Animals; Blood Pressure; Cardiomegaly; Cardiovascular Agents; Endothelin-1; Hypertension, Renal; Male; Myocardium; Nephrectomy; Nitric Oxide; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes

The present study evaluated the contribution of cytochrome P-450 omega-hydroxylase in modulating the reactivity of cremaster muscle arterioles in normotensive rats on high-salt (HS) and low-salt (LS) diet and in rats with reduced renal mass hypertension (RRM-HT). Changes in arteriolar diameter in response to ACh, sodium nitroprusside (SNP), ANG II, and elevated O(2) were measured via television microscopy under control conditions and following cytochrome P-450 omega-hydroxylase inhibition with 17-octadecynoic acid (17-ODYA) or N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS). In normotensive rats on either LS or HS diet, resting tone was unaffected and arteriolar reactivity to ACh or SNP was minimally affected by cytochrome P-450 omega-hydroxylase inhibition. In RRM-HT rats, cytochrome P-450 omega-hydroxylase inhibition reduced resting tone and significantly enhanced arteriolar dilation to ACh and SNP. Treatment with 17-ODYA or DDMS inhibited arteriolar constriction to ANG II and O(2) in all the groups, although the degree of inhibition was greater in RRM-HT than in normotensive animals. These results suggest that metabolites of cytochrome P-450 omega-hydroxylase contribute to the altered reactivity of skeletal muscle arterioles to vasoconstrictor and vasodilator stimuli in RRM-HT.

Topics: Acetylcholine; Amides; Angiotensin II; Animals; Arterioles; Blood Pressure; Cardiovascular Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Enzyme Inhibitors; Fatty Acids, Unsaturated; Hydroxyeicosatetraenoic Acids; Hypertension, Renal; Male; Microscopy, Video; Mixed Function Oxygenases; Muscle, Skeletal; Nitroprusside; Oxygen; Perfusion; Rats; Rats, Sprague-Dawley; Sodium Chloride, Dietary; Sulfones