cardiovascular-agents and Hypertension--Renovascular

Atherosclerotic renovascular disease is an increasingly recognized cause of severe hypertension and declining kidney function. Patients with atherosclerotic renovascular disease have been demonstrated to have an increased risk of adverse cardiovascular events. Over the course of the last two decades renal artery revascularization for treatment of atherosclerotic renal artery stenosis (RAS) has gained great increase via percutaneous techniques. However the efficacy of contemporary revascularization therapies in the treatment of renal artery stenosis is unproven and controversial. The indication for renal artery stenting is widely questioned due to a not yet proven benefit of renal revascularization compared to best medical therapy. Many authors question the efficacy of percutaneous renal revascularization on clinical outcome parameters, such as preservation of renal function and blood pressure control. None of the so far published randomized controlled trials could prove a beneficial outcome of RAS revascularization compared with medical management. Currently accepted indications for revascularization are significant RAS with progressive or acute deterioration of renal function and/or severe uncontrollable hypertension, renal function decline with the use of agents blocking the renin-angiotensin system and recurrent flash pulmonary edema. The key point for success is the correct selection of the patient. This article summarizes the background and the limitations of the so far published and still ongoing controlled trials.

Topics: Angioplasty; Blood Pressure; Cardiovascular Agents; Evidence-Based Medicine; Humans; Hypertension, Renovascular; Randomized Controlled Trials as Topic; Renal Artery Obstruction; Risk Assessment; Risk Factors; Stents; Treatment Outcome

Atherosclerotic renovascular disease (aRVD) is an increasingly recognized cause of severe hypertension and declining kidney function. Patients with aRVD have been demonstrated to have an increased risk of adverse cardiovascular events compared with patients without aRVD. For these reasons, >45,000 renal artery revascularization procedures are performed annually, with significant growth observed in the number of procedures performed each year. The efficacy of contemporary revascularization therapies in the treatment of aRVD is unproven and controversial, with no level I data to support current practices. Lower-level data suggest that kidney function improvement is a key indicator of subsequent improved survival free of adverse cardiovascular events and dialysis, and that observed improvements of hypertension confer, at best, limited benefit. This review focuses on existing data on the management of aRVD, including data from completed and ongoing randomized clinical trials. This review also examines other existing data regarding aRVD that may guide current treatment and future research efforts into this significant clinical and public health problem until widely accepted level I evidence emerges.

Topics: Angioplasty; Atherosclerosis; Cardiovascular Agents; Disease Progression; Evidence-Based Medicine; Humans; Hypertension, Renovascular; Kidney; Patient Selection; Randomized Controlled Trials as Topic; Renal Artery Obstruction; Renal Dialysis; Stents; Treatment Outcome; Vascular Surgical Procedures

Patients with atherosclerotic renal artery stenosis may develop hypertension, recurrent pulmonary edema and chronic renal failure, but have a much higher risk of dying from stroke or myocardial infarction than of progressing to end-stage renal disease. Indeed, atherosclerotic renal artery stenosis typically occurs in high risk patients with coexistent vascular disease elsewhere. Recent controlled trials comparing medication to revascularization have shown that only a minority of such patients can expect hypertension cure, whereas the results of trials designed to document the ability of revascularization to prevent progressive renal failure are not yet available. Revascularization should be undertaken in patients with atherosclerotic renal artery stenosis and resistant hypertension or heart failure, and probably in those with rapidly deteriorating renal function or with an increase in plasma creatinine levels during angiotensin-converting enzyme inhibition, especially if their renal resistance--index before revascularization is less than 80. With or without revascularization, medical therapy using antihypertensive agents, statins and aspirin is necessary in almost all cases.

Topics: Angiotensin-Converting Enzyme Inhibitors; Arteriosclerosis; Aspirin; Cardiovascular Agents; Combined Modality Therapy; Creatinine; Diagnostic Imaging; Drug Therapy, Combination; Heart Failure; Humans; Hypertension, Renovascular; Hypolipidemic Agents; Myocardial Infarction; Platelet Aggregation Inhibitors; Pulmonary Edema; Radionuclide Imaging; Renal Artery; Renal Artery Obstruction; Risk Factors; Stroke

Topics: Aged; Angiography; Arterial Occlusive Diseases; Cardiovascular Agents; Delayed Diagnosis; Diagnosis, Differential; Female; Heart Failure; Hemodiafiltration; Humans; Hypertension; Hypertension, Renovascular; Iliac Artery; Kidney Transplantation; Postoperative Complications; Renal Artery Obstruction; Reoperation; Stents; Ultrasonography, Doppler

Imbalanced matrix metalloproteinase (MMP)-2 activity and transforming growth factor expression (TGF-β) are involved in vascular remodeling of hypertension. Atorvastatin and sildenafil exert antioxidant and pleiotropic effects that may result in cardiovascular protection. We hypothesized that atorvastatin and sildenafil alone or in association exert antiproliferative effects by down-regulating MMP-2 and TGF-β, thus reducing the vascular hypertrophy induced by two kidney, one clip (2K1C) hypertension. Sham and 2K1C rats were treated with oral atorvastatin 50 mg/kg, sildenafil 45 mg/kg, or both, daily for 8 weeks. Blood pressure was monitored weekly. Morphologic changes in the aortas were studied. TGF-β levels were determined by immunofluorescence. MMP-2 activity and expression were determined by in situ zymography, gel zymography, Western blotting, and immunofluorescence. The effects of both drugs on proliferative responses of aortic smooth muscle cells to PDGF and on on MMP-2 activity in vitro were determined. Atorvastatin, sildenafil, or both drugs exerted antiproliferative effects in vitro. All treatments attenuated 2K1C-induced hypertension and prevented the increases in the aortic cross-sectional area and media/lumen ratio in 2K1C rats. Aortas from 2K1C rats showed higher collagen deposition, TGF-β levels and MMP-2 activity and expression when compared with Sham-operated animals. Treatment with atorvastatin and/or sildenafil was associated with attenuation of 2K1C hypertension-induced increases in these pro-fibrotic factors. However, these drugs had no in vitro effects on hr-MMP-2 activity. Atorvastatin and sildenafil was associated with decreased vascular TGF-β levels and MMP-2 activity in renovascular hypertensive rats, thus ameliorating the vascular remodeling. These novel pleiotropic effects of both drugs may translate into protective effects in patients.

Topics: Animals; Aorta; Atorvastatin; Cardiovascular Agents; Collagen; Disease Models, Animal; Drug Combinations; Drug Synergism; Endothelium, Vascular; Gene Expression Regulation; Hypertension, Renovascular; Male; Matrix Metalloproteinase 2; Myocytes, Smooth Muscle; Oxidative Stress; Platelet-Derived Growth Factor; Rats; Rats, Wistar; Reactive Oxygen Species; Signal Transduction; Sildenafil Citrate; Transforming Growth Factor beta; Vascular Remodeling

The objective of this study was to analyze the use of sirolimus-eluting stent (SES) placement for the treatment of renal artery in-stent restenosis (RA-ISR). The optimal treatment of RA-ISR has not been fully elucidated to date. We retrospectively analyzed consecutive patients from our institution who underwent treatment of RA-ISR with a SES from May 2004 to June 2006. Using duplex ultrasound, RA-ISR (> 60% diameter) was determined by peak systolic velocity (PSV) > 300 cm/s and renal aortic ratio (RAR) > 4.0. Renal function (creatinine) and blood pressure were measured at baseline and follow-up. SESs were implanted in 16 patients (22 renal arteries) during the study period. The study cohort was predominantly female (75%) with a mean age of 68 +/- 12 years. RA-ISR was treated with SESs with a mean diameter of 3.5 mm and mean length of 17.9 +/- 3.8 mm. The mean post-dilation balloon diameter was 4.8 +/- 0.6. The baseline renal artery PSV was 445 +/- 131 cm/s with a mean RAR of 5.0 +/- 1.6. Follow-up information was available in 21 renal arteries. During a median follow-up of 12 months (range: 9-15 months), 15 renal arteries (71.4%) developed recurrence of ISR by ultrasonographic criteria. Univariate analysis revealed that female sex was an independent predictor of recurrence of ISR after SES implantation (p < 0.05). In conclusion, placement of a SES for the treatment of ISR in renal arteries is associated with high initial technical success but significant restenosis on duplex ultrasonography at follow-up.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon; Cardiovascular Agents; Drug-Eluting Stents; Female; Hemodynamics; Humans; Hypertension, Renovascular; Kidney; Male; Middle Aged; Radiography; Recurrence; Renal Artery Obstruction; Retrospective Studies; Risk Assessment; Risk Factors; Sirolimus; Stents; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Duplex

The adaptive changes that develop in the pressure-overloaded left ventricular myocardium include cardiac hypertrophy and interstitial fibrosis. The objectives of the present study were to evaluate the effects of Tanshinone II-A, a bioactive diterpene quinone isolated from Danshen, on cardiac fibrosis and collagen metabolism in rats with renovascular hypertension. Male Sprague-Dawley rats were subjected to two-kidney two-clip (2K2C) or sham operation (sham) and treated with Valsartan (Val, 26.7 mg/kg/d), Tanshinone II-A (Tsn, 70, 35 mg/kg/d) or vehicle. Six weeks later, systolic blood pressure (BP), LV weight, collagen abundance, cardiac function parameters, hydroxyproline content and mRNA levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 were evaluated. Both high-dose (Tsn-H, 70 mg/kg/d) and low-dose (Tsn-L, 35 mg/kg/d) of Tsn failed to attenuate 2K2C-induced BP elevation but significantly attenuated the attendant interstitial fibrosis. Val suppressed elevations of BP and left ventricular systolic pressure (LVSP) in 2K2C rats. Val and Tsn-H exerted comparable suppressive effects on the gene expression of MMP-9 and TIMP-1, while Val decreased the MMP-2 mRNA level without affecting the transcript levels of TIMP-2. Both Val and Tsn-H attenuated cardiac dysfunction, while Tsn-L showed slight improvement. These data demonstrate for the first time, that Tsn prevented cardiac fibrosis and improved cardiac function in a rat model of renovascular hypertensive independent of hypotensive effect. Tsn conferred its beneficial effects on the collagen metabolism probably through its regulation of transcript levels of the MMPs/TIMPs balance.

Topics: Abietanes; Animals; Blood Pressure; Cardiovascular Agents; Collagen; Drugs, Chinese Herbal; Fibrosis; Gene Expression; Heart; Hypertension, Renovascular; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Myocardium; Phytotherapy; Rats; Rats, Sprague-Dawley; RNA, Messenger; Salvia miltiorrhiza; Tetrazoles; Tissue Inhibitor of Metalloproteinase-1; Valine; Valsartan

Renal artery stenosis may cause or exacerbate hypertension and renal failure. Percutaneous transluminal renal artery stent placement, increasingly the first-line therapy for ostial atherosclerotic renal artery stenosis, can be complicated by in-stent restenosis weeks to months after the procedure. There is currently no consensus for the treatment of in-stent restenosis. Sirolimus-eluting stents have been shown to be effective to treat in-stent restenosis in the coronary circulation. We report a case of sustained 24-month patency after repair of recurrent renal artery in-stent restenosis with use of a sirolimus-eluting stent.

Topics: Aged; Angioplasty, Balloon; Cardiovascular Agents; Drug-Eluting Stents; Humans; Hypertension, Renovascular; Male; Metals; Prosthesis Design; Radiography; Renal Artery Obstruction; Secondary Prevention; Sirolimus; Stents; Time Factors; Treatment Outcome; Vascular Patency

Studies performed in experimental animals and in humans have documented that high blood pressure markedly impairs baroreceptor control of heart rate. Whether a similar impairment also characterizes baroreceptor control of sympathetic activity modulating peripheral vasomotor tone is still unknown. In 28 untreated essential hypertensive subjects [14 of moderate and 14 of more severe degree, age 51.6+/-2.4 and 52.6+/-2.1 years (mean+/-SEM)] and in 13 untreated secondary hypertensives (renovascular or pheochromocytoma, age 50.1+/-4.6 years), we measured beat-to-beat arterial blood pressure (finger photoplethysmographic device), heart rate (electrocardiogram), and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Data were compared with those obtained in 15 age-matched normotensive control subjects. Muscle sympathetic nerve activity (bursts per 100 heart beats) showed a progressive and significant (P<.01) increase from normotension (40.3+/-3.3) to moderate (55.6+/-4.1) and more severe essential hypertension (68.2+/-4.1), paralleling the progressive increase in blood pressure values. In contrast, muscle sympathetic nerve activity was not increased in secondary hypertensives (40.5+/-6.7) despite blood pressure values similar to or even greater than those of severe essential hypertensives. In both essential and secondary hypertensives, baroreceptor-heart rate control was displaced toward elevated blood pressure values and markedly impaired compared with normotensive subjects (average reduction, 38.5%). In contrast, the sympathoinhibitory and sympathoexcitatory responses to baroreceptor stimulation and deactivation were displaced toward elevated blood pressure values but similar in all groups. Thus, sympathetic activation characterizes essential but not secondary hypertension. Regardless of its nature, however, hypertension is not accompanied by an impairment of baroreceptor modulation of sympathetic activity.

Topics: Blood Pressure; Cardiovascular Agents; Case-Control Studies; Female; Heart Rate; Humans; Hypertension; Hypertension, Renovascular; Male; Middle Aged; Muscle, Skeletal; Nitroprusside; Phenylephrine; Pheochromocytoma; Pressoreceptors; Sympathetic Nervous System