Current Hypertension Reviews

ISSN: 1573-4021

Current Hypertension Reviews
Volume 6, Number 3, August 2010

Contents


Renal Solute Transporters and Their Relevance to Serum Urate Disorder Pp. 148-154
Naohiko Anzai, Promsuk Jutabha and Hitoshi Endou
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Platelet Ca²⁺ATPases: Identification and Regulation in Hypertension Pp. 155-165
Régis Bobe, Saoussen Dally, Chiraz Chaabane, Elisabeth Corvazier, Evelyne Polidano, Raymonde Bredoux and Jocelyne Enouf
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Hypertension in Older Patients Pp. 166-172
Firas A. Ghanem and Assad Movahed
[Abstract] [Purchase Article]


Irbesartan: Second Generation of ARB as Metabosartan Pp. 173-179
Ryuichi Morishita, Yasuhiko Kanda and Masatoshi Nakajima
[Abstract] [Purchase Article]


Antihypertensive Properties of Angiotensin-Converting Enzyme Inhibitors (ACEI) Independent of the Renin-Angiotensin System Pp. 180-185
Therezinha B. Paiva, Jamille C. R. Bravo, Nelson C. Farias and Teresa Feres
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Tissue Factor and Hypertension Pp. 186-189
Alessandro Celi, Alessandra Del Fiorentino, Silvana Cianchetti, Giulia Dell’Omo and Roberto Pedrinelli
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Resurgence of Herbal Antihypertensives in Management of Hypertension Pp. 190-198
Rajkumar Verma, Kashif Hanif, Dinakar Sasmal and Ram Raghubir
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Role of PGE₂ in Blood Pressure Regulation Pp. 199-209
Tianxin Yang
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Renal Artery Stenosis: Current Perspectives on Imaging and Endovascular Management Pp. 210-221
Sandeep Vaidya, Manjiri Dighe and Xiaoming Yang
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Abstracts


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Renal Solute Transporters and Their Relevance to Serum Urate Disorder
Naohiko Anzai, Promsuk Jutabha and Hitoshi Endou

Since uric acid (urate), the final product of purine metabolism, exhibits antioxidative activity, its protective role against oxidative stress becomes attractive. Low serum urate levels have been associated with multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease. Despite its beneficial role, hyperuricemia is associated with gout, hypertension, cardiovascular diseases such as myocardial infarction and stroke, and renal diseases such as acute urate nephropathy and nephrolithiasis. The urate transport system of the kidney is an important determinant of the serum urate level, but clarification of its molecular mechanism remains incomplete. In 2002, our group identified URAT1 (SLC22A12), a renal apical urate/anion exchanger, leading to the accumulation of information concerning individual molecules involved in urate transport in the kidney. In 2008, we functionally characterized facilitatory glucose transporter family member GLUT9 (SLC2A9) as a voltage-driven urate transporter URATv1 and analysis of a renal hypouricemia patient with a genetic defect in SLC2A9 have established the main route of the urate reabsorption pathway at the basolateral side of renal proximal tubules, where urate in the urinary lumen is taken up via apical URAT1 and intracellular urate exits from the cell to the interstitium/blood space via basolateral URATv1. In this review, recent findings concerning these molecules are presented.


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Platelet Ca²⁺ATPases: Identification and Regulation in Hypertension
Régis Bobe, Saoussen Dally, Chiraz Chaabane, Elisabeth Corvazier, Evelyne Polidano, Raymonde Bredoux and Jocelyne Enouf

Cell activation, proliferation, differentiation and apoptosis are tidily regulated by calcium signals. Altered Ca²⁺ handling has been described in essential hypertension in different cells including platelets. In this review we will particularly focus on members of calcium pump family; the plasma membrane Ca²⁺ATPases (PMCAs) and the Sarco/ Endoplasmic Reticulum Ca²⁺ATPases (SERCAs) that are expressed in platelets. We will describe recently identified isoforms present in platelets and the regulation of their expressions along both human and rat essential hypertensions. Moreover, results suggesting that platelet Ca²⁺ATPase expressions in hypertensive patients can sign an abnormal megakaryocytopoiesis in this pathology will be presented and discussed.


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Hypertension in Older Patients
Firas A. Ghanem and Assad Movahed

Hypertension is most prevalent in the elderly population and a major source of morbidity and mortality. After the age of 50 years, systolic pressure continues to rise and diastolic pressure tends to fall leading to the predominance of isolated systolic hypertension (ISH). Systolic blood pressure is the main determinant of risk and should be the target of drug therapy. Lowering blood pressure in the elderly tends to decrease the incidence of stroke, heart failure and myocardial infarction. Life style and dietary modifications, in addition to low sodium diet help achieve blood pressure goals. In the absence of a compelling indication, a low dose thiazide diuretic or a long-acting dihydropyridine calcium channel blocker are appropriate first line therapies. Inhibitors of the Renin-Angiotensin-Aldosterone System (RAAS) are appropriate alternatives and could be added or substituted. β blockers may not be appropriate as monotherapy or first line treatment. Combination therapy is frequently needed and the use of low dose combinations may help reduce adverse effects. Goals of therapy may be similar to those in younger populations, although achieving blood pressure goals may be challenging.


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Irbesartan: Second Generation of ARB as Metabosartan
Ryuichi Morishita, Yasuhiko Kanda and Masatoshi Nakajima

Irbesartan is an angiotensin II subtype 1 (AT₁) receptor blocker (ARB) that inhibits the actions of angiotensin II on the renin-angiotensin-aldosterone system. Once-daily administration of irbesartan provides 24-hour control of blood pressure in hypertensive patients. A renoprotective effect of irbesartan in hypertensive patients with type 2 diabetes at both the early and later stages of diabetic nephropathy has been demonstrated in two large, randomized, double-blind, placebo-controlled, multinational trials: the Irbesartan Microalbuminuria Type 2 Diabetes in Hypertensive Patients (IRMA 2) trial and the Irbesartan Diabetic Nephropathy Trial (IDNT). In addition to the angiotensin II antagonistic activity, irbesartan shows partial PPARγ agonistic activity and is highly distributed to the kidney, the heart and white adipose tissue. Indeed, ARBs which have partial PPARγ agonistic activity such as irbesartan and termisartan have been reported to improve insulin resistance and lipid profiles in diabetes mellitus patients as well as metabolic syndrome patients. Thus, a class of ARB which has partial PPARγ agonistic activity might be termed as “metabosartan”. Beneficial therapeutic efficacy of irbesartan in hypertensive patients might result from substantial dual AT₁ receptor antagonist/ PPARγ agonist actions and relatively high concentration in end-target tissues. Here, we summarized the potential therapeutic values of irbesartan.


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Antihypertensive Properties of Angiotensin-Converting Enzyme Inhibitors (ACEI) Independent of the Renin-Angiotensin System
Therezinha B. Paiva, Jamille C. R. Bravo, Nelson C. Farias and Teresa Feres

Angiotensin converting enzyme inhibitors (ACEi) lead to inhibition of angiotensin II formation and bradykinin inactivation. However, ACEi also have antihypertensive activity that is independent of the renin-angiotensin system. For example, the enhanced peripheral resistance due to smooth muscle cell hypertrophy and hyperplasia (related to lower apoptosis) increases vascular tonus in established hypertension. ACEi treatment restores susceptibility to apoptosis in these cells through stimulation of the Bax protein. Also, an altered function of the Na⁺/K⁺ ATPase leads to elevated levels of intracellular sodium concentration, and depolarization of smooth muscle membranes increasing their excitability. ACEi treatment normalizes this pump function, and the arterial tonus by release of endothelial nitric oxide and prostacyclin. Endothelium-dependent hyperpolarization (to acetylcholine) in mesenteric arteries mediated by release of the endothelium-derived hyperpolarizing factor, is impaired in hypertensive humans and animals. In this instance, ACEi restored this im-paired response, since this treatment causes vascular remodeling in resistance SHR arteries through induction of apoptosis of vascular smooth muscle cells reducing the subendothelial thickening, which improves the EDHF circulation. The purpose of this review is to analyze the performance of ACEi in normalizing the vascular tonus during the hypertensive state, which may render new perspectives in basic and clinical research for the next years.


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Tissue Factor and Hypertension
Alessandro Celi, Alessandra Del Fiorentino, Silvana Cianchetti, Giulia Dell’Omo and Roberto Pedrinelli

Hypertension is characterized by an increased risk of thrombotic complications. This reviews describes the possible roles of tissue factor in the increased risk of thrombosis in hypertensive patients. Tissue factor is an integral membrane protein that represents the physiologic initiator of blood coagulation; its roles in thrombosis are also well documented. Activation of the renin angiotensin system may modulate tissue factor expression as shown by the stimulation brought about by Angiotensin II in human monocytes and smooth muscle cells, and in rat aortic endothelial cells and the inhibition obtained by renin angiotensin system blockade through angiotensin converting enzyme blockers, angiotensin type II receptor antagonists and direct renin inhibitors. Finally, in clinical trials, administration of angiotensin type 1 receptor antagonists to hypertensive patients reduced circulating tissue factor. P-selectin, an adhesion receptor expressed by activated platelets and endothelial cells, upregulates tissue factor synthesis by human monocytes. Since platelet activation accompanies hypertension, induction of tissue factor synthesis mediated, perhaps, by P-selectin may represent a further link between hypertension and thrombosis. Pharmacological interventions that reduce TF upregulation might contribute to reduce the risk of cardiovascular complications in these patients.


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Resurgence of Herbal Antihypertensives in Management of Hypertension
Rajkumar Verma, Kashif Hanif, Dinakar Sasmal and Ram Raghubir

Hypertension is one of the major cardiovascular problems and causes a number of vascular disorders. Until the 1940s majority of the diseases were treated by traditional drugs obtained from plants/herbs only. Even the first potent herbal antihypertensive was obtained from root of Rauwolfia serpentina, a famous Ayurvedic plant but soon the modern antihypertensives took the center-stage because of their precise, defined and fast action. However, due to their growing adverse effects, interest in the use of these drugs also gradually started waning. This has lead to the resurgence of marked awareness about traditional medicines and a considerable renewed global interest in the plant based drugs. Much emphasis is now being given to validate the extract/fraction as well as single molecules obtained from plant resources based on their traditional claims. In this review, we have laid emphasis on the mechanistic aspect of antihypertensive effect of some medicinal plants and their therapeutic use. We have further tried to shed light on the attempts being made for the validation and documentation of traditional plants and herbs for their future development as potential therapy in hypertension.

What’s already known?

• The herbal medications had been used since long to treat various cardiovascular disorders including high blood pressure before the arrival of modern therapy.

• Global interest has now been renewed in herbal medicines but need authentication and validation in support of their therapeutic value.

What this article may add?

• This review emphasizes the mechanistic aspect of herbal medicines, their therapeutic values in clinical situation as well as present measures and recent approaches to validate and document their antihypertensive efficacies.


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Role of PGE₂ in Blood Pressure Regulation
Tianxin Yang

Prostaglandin E₂ (PGE₂) participates in blood pressure (BP) regulation through diverse mechanisms involving different tissues and different receptor subtypes. In general, PGE₂ functions as a natriuretic factor in the kidney, promoting sodium excretion via inhibition of sodium transport in the distal nephron. On the other hand, PGE₂ is a vasoactive agent capable of modulating vascular tone. PGE₂ is a product of prostaglandin E synthase (PGES) and its biologic action is mediated by four EP receptors EP1-4 which exhibit distinct vasoactive properties. The best characterized PGES is microsomal prostaglandin E synthase-1 (mPGES-1), a viable target for the next generation of analgesic drugs. The review will focus on recent advances in understanding the roles of mPGES-1 and EP receptors in BP regulation.


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Renal Artery Stenosis: Current Perspectives on Imaging and Endovascular Management
Sandeep Vaidya, Manjiri Dighe and Xiaoming Yang

Renal artery stenosis in its early phase is now considered a treatable cause of hypertension. The most common causes of renal artery stenosis (RAS) are atherosclerosis and fibromuscular dysplasia. It is important to be familiar with the various modalities for diagnosis as well as treatment of RAS, especially due to the increasing availability of minimally invasive therapies. These diagnostic modalities include ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and nuclear medicine scans. RAS if not treated leads to progressive development of renal insufficiency and renal failure. The minimally invasive therapies for treatment of RAS include percutaneous balloon angioplasty and stent placement. The objective of this article is to provide an overview of the diagnosis of renal arterial stenosis using newer imaging technology, as well as to familiarize the readers with the advances made in the realm of endovascular treatment.