Mesenchymal stem cells (MSC) prevented the progression of renovascular hypertension, improved renal function and architecture.

Renovascular hypertension induced by 2 Kidney-1 Clip (2K-1C) is a renin-angiotensin-system (RAS)-dependent model, leading to renal vascular rarefaction and renal failure. RAS inhibitors are not able to reduce arterial pressure (AP) and/or preserve the renal function, and thus, alternative therapies are needed. Three weeks after left renal artery occlusion, fluorescently tagged mesenchymal stem cells (MSC) (2×10(5) cells/animal) were injected weekly into the tail vein in 2K-1C hypertensive rats. Flow cytometry showed labeled MSC in the cortex and medulla of the clipped kidney. MSC prevented a further increase in the AP, significantly reduced proteinuria and decreased sympathetic hyperactivity in 2K-1C rats. Renal function parameters were unchanged, except for an increase in urinary volume observed in 2K-1C rats, which was not corrected by MSC. The treatment improved the morphology and decreased the fibrotic areas in the clipped kidney and also significantly reduced renal vascular rarefaction typical of 2K-1C model. Expression levels of IL-1ß, TNF-α angiotensinogen, ACE, and Ang II receptor AT1 were elevated, whereas AT2 levels were decreased in the medulla of the clipped kidney. MSC normalized these expression levels. In conclusion, MSC therapy in the 2K-1C model (i) prevented the progressive increase of AP, (ii) improved renal morphology and microvascular rarefaction, (iii) reduced fibrosis, proteinuria and inflammatory cytokines, (iv) suppressed the intrarenal RAS, iv) decreased sympathetic hyperactivity in anesthetized animals and v) MSC were detected at the CNS suggesting that the cells crossed the blood-brain barrier. This therapy may be a promising strategy to treat renovascular hypertension and its renal consequences in the near future.

Interventional treatment of hypertension: a new paradigm.

Hypertension is thought to contribute to more than 7 million deaths worldwide each year and contributes to the development of atherosclerotic lesions that lead to myocardial infarction and stroke. While lifestyle modifications (diet, exercise, weight loss) and pharmacotherapy have been proven to be effective in the treatment of hypertension, as many as half of patients have uncontrolled BP and remain at risk for elevated cardiovascular morbidity and mortality. The main physiologic targets for interventional treatment include alteration of blood flow to the kidney, activation of the carotid baroreflex system, and modification of the renal sympathetic nervous system. The results of prior studies and new studies of interventional treatments of resistant hypertension are covered in this review.

[Drug-independent blood pressure control through the autonomous nervous system]. / Nicht-medikamentöse Hypertoniebehandlung durch Beeinflussung des autonomen Nervensystems.

Arterial hypertension is a chronic disease with a therapeutical challenge for the patient and the physician involved. Patient-independent techniques with good efficacy and tolerability are wanted. The autonomous nervous system insufficiently therapeutically exploited to date, is now approachable by two types of intervention: renal nerve ablation, an endovascular approach without remaining foreign body, and BAT, baroreflex activating therapy using an implantable device stimulating the carotid sinus. The blood pressure lowering potency of BAT appears more than with renal nerve ablation and also clinical study data are more prevalent. With both treatment options the patients having the most profit are insufficiently defined. Given this knowledge, any form of secondary hypertension needs to be excluded beforehand.

Increased endogenous H2S generation by CBS, CSE, and 3MST gene therapy improves ex vivo renovascular relaxation in hyperhomocysteinemia.

Hydrogen sulfide (H(2)S) has recently been identified as a regulator of various physiological events, including vasodilation, angiogenesis, antiapoptotic, and cellular signaling. Endogenously, H(2)S is produced as a metabolite of homocysteine (Hcy) by cystathionine ß-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST). Although Hcy is recognized as vascular risk factor at an elevated level [hyperhomocysteinemia (HHcy)] and contributes to vascular injury leading to renovascular dysfunction, the exact mechanism is unclear. The goal of the current study was to investigate whether conversion of Hcy to H(2)S improves renovascular function. Ex vivo renal artery culture with CBS, CSE, and 3MST triple gene therapy generated more H(2)S in the presence of Hcy, and these arteries were more responsive to endothelial-dependent vasodilation compared with nontransfected arteries treated with high Hcy. Cross section of triple gene-delivered renal arteries immunostaining suggested increased expression of CD31 and VEGF and diminished expression of the antiangiogenic factor endostatin. In vitro endothelial cell culture demonstrated increased mitophagy during high levels of Hcy and was mitigated by triple gene delivery. Also, dephosphorylated Akt and phosphorylated FoxO3 in HHcy were reversed by H(2)S or triple gene delivery. Upregulated matrix metalloproteinases-13 and downregulated tissue inhibitor of metalloproteinase-1 in HHcy were normalized by overexpression of triple genes. Together, these results suggest that H(2)S plays a key role in renovasculopathy during HHcy and is mediated through Akt/FoxO3 pathways. We conclude that conversion of Hcy to H(2)S by CBS, CSE, or 3MST triple gene therapy improves renovascular function in HHcy.

Acupuncture reduces experimental renovascular hypertension through mechanisms involving nitric oxide synthases.

OBJECTIVE: To test the hypothesis that acupuncture on stomach 36 point (ST-36) reduces hypertension by activating nitric oxide synthase signaling mechanisms. METHODS: The authors used the two-kidney, one-clip renal hypertension (2K1C) hamster model with electroacupuncture treatment. RESULTS: Thirty-minute daily electroacupuncture treatment for 5 days reduced mean arterial pressure from 160.0 +/- 7.6 to 128.0 +/- 4.3 mmHg (mean +/- SEM), compared to 115.0 +/- 7.2 mmHg in sham-operated hamsters. Electroacupuncture increased periarteriolar NO concentration from 309.0 +/- 21.7 nM to 417.9 +/- 20.9 nM in the 2K1C hamster cheek pouch microcirculation when measured with NO-sensitive microelectrodes. Hypertension reduced endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) proteins relative to the sham-operated control, as measured by Western blotting. Electroacupuncture prevented the reduction of eNOS and nNOS associated with hypertension and showed even higher eNOS and nNOS expressions than sham-operated control in stomach and cheek pouch tissues, which are on the stomach meridian. Analysis of liver tissue, a non-stomach-meridian organ, indicated that electroacupuncture did not have a significant benefit in terms of enhanced expressions of eNOS and nNOS in the treated 2K1C hypertensive group. CONCLUSIONS: Activation of eNOS and nNOS is one of the mechanisms through which ST-36 electroacupuncture reduces blood pressure; this reduction works through the stomach meridian.

Incorporating patient-centered outcomes in the analysis of cost-effectiveness: imaging strategies for renovascular hypertension.

OBJECTIVE: Our aim was to assess the contribution of patient-centered short-term disutilities and quality-of-life measures in the cost-effectiveness analysis of CT angiography, MR angiography, and conventional angiography in patients with medication-resistant hypertension. MATERIALS AND METHODS: A decision analytic model compared the life expectancy and incremental cost per life year using three initial diagnostic tests in a cohort of hypothetical individuals with medication-resistant hypertension over a range of renal artery stenosis probabilities: CT angiography (sensitivity, 96%; specificity, 96%; cost, $865); MR angiography (98%, 94%, $850); and conventional angiography (99%, 99%, $2,627). All imaging strategies were compared with a base case scenario mimicking the natural history of medication-resistant hypertension and with a scenario immediate enhanced medical therapy without prior imaging. Individuals without evidence of renal artery stenosis on initial testing underwent conventional angiography if enhanced medical therapy failed to control hypertension. Individuals diagnosed with renal artery stenosis on MR angiography required conventional angiography for definitive stent treatment ($11,1223). Blood pressure response to renal artery stenting or enhanced medical therapy varied according to blood pressure, as did the incidence of myocardial infarction and stroke resulting from hypertension. Patients who progressed to end-stage renal disease received dialysis ($60,000 per year). Quality-of-life adjustments were made for patients with hypertension, end-stage renal disease, myocardial infarction, and stroke. Short-term disutilities from undergoing an imaging test were included. The analysis accounted for direct costs derived from Medicare reimbursements and total costs derived from the literature. RESULTS: All imaging strategies were cost-effective compared with enhanced medical therapy alone or with natural history. When only direct costs were considered, MR angiography was the preferred strategy, with conventional angiography as a cost-effective alternative to MR angiography. When total costs were considered, conventional angiography dominated all other strategies. Adjusting for quality of life decreased the incremental cost-effectiveness ratios, making an already competitive strategy a more favorable alternative to the base case. Adjusting for test-related disutility did not significantly influence the cost-effectiveness of any of the imaging tests. Despite marked variation in the key clinical and cost variables, MR angiography remained the most cost-effective strategy. CONCLUSION: In the evaluation and treatment of medication-resistant hypertension, strategies that included preliminary imaging saved more lives than did the immediate institution of enhanced medical therapy at a lesser cost.

Diagnosis and evaluation of secondary hypertension.

Although patients with secondary hypertension comprise only a small percentage of those with elevated blood pressure, this subgroup should not be ignored. In many cases, correcting the cause of secondary hypertension can lead to a cure, thus avoiding the need for long-term medical therapy, with its attendant risks and economic toll. Moreover, effective treatment of secondary hypertension can prevent chronic complications, such as left ventricular hypertrophy and coronary artery disease, which markedly increase morbidity and mortality. Nearly all forms of secondary hypertension are related to decreased renal function and/or derangement of hormonal balance or secretion. If hypertension is secondary to chronic renal failure of any etiology, it can be recognized from biochemical assays for blood urea nitrogen and creatinine.

Percutaneous transluminal angioplasty for treatment of renovascular hypertension.

Four patients with typical renovascular hypertension due to atherosclerotic stenosis (3 patients) and near occlusion (one patient) were treated with percutaneous transluminal angioplasty (PTA). Two patients had malignant hypertension by clinical standards. All had significant reduction in blood pressure following angioplasty, resulting in either a normotensive state, or management with significantly less antihypertensive medication. Patency and normal renin levels were achieved within two months in 2 patients. Clinical follow-up documented continued reduction in blood pressure. Advantages of the procedure include local anesthesia, relatively little discomfort, repeatability, and the fact that surgery is not precluded if angioplasty is unsuccessful.