Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixty million Americans have hypertension, a major cardiovascular risk factor. Its presence accelerates the atherosclerotic process, producing strokes, heart attacks, heart failure, renal failure, and peripheral vascular disease. This article highlights the historical landmarks in the study of this disease from the first documented measurement of blood pressure in 1733, through the most recent pharmacologic approaches to treatment. In addition, the roles of the kidney and the renin-angiotensin-aldosterone system are examined.
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PMID:Historical reflections on hypertension. 194 83

Hypertension is common in hemodialyzed patients and constitutes an important cardiovascular risk factor. Fluid retention, inappropriate stimulation of the renin-angiotensin system, sympathetic overactivity and changes of vessel wall structure have been shown to be important factors in its pathogenesis. It has been claimed that hemofiltration permits a better control of hypertension in the interdialytic interval, although the evidence is not perfectly convincing; blood pressure tends to be lower with continuous ambulatory peritoneal dialysis. While fluid withdrawal and - within certain limits - adjustment of dialysate sodium concentration constitutes a primary line of therapy, antihypertensive medication is necessary in approximately 20% of patients. Specific problems with dialysis patients are cumulation of drugs (some cardioselective beta-blockers, alpha-methyldopa, captopril), altered dose-response relationship (diuretics) and particularly interaction with cardiovascular stability during fluid withdrawal.
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PMID:Treatment of hypertension in dialysis patients. 286 71

Hypertension is an important cardiovascular risk factor. High blood pressure per se is not a disease but a hemodynamic alteration associated with vascular disease. Two classes of drugs are especially effective in lowering blood pressure and preventing cardiovascular complications, angiotensin converting enzyme (ACE) inhibitors and calcium antagonists. The hemodynamic effects of ACE inhibitors and calcium antagonists are complementary. While ACE inhibitors inhibit the renin-angiotensin system and reduce sympathetic outflow, calcium antagonists dilate large conduit and resistance arteries. Certain calcium antagonists, such as verapamil, lower heart rate. In the blood vessel wall, the local vascular effects of ACE inhibitors and calcium antagonists are also complementary. While ACE inhibitors inhibit activation of angiotensin I into angiotensin II and prevent the breakdown of bradykinin (which stimulates nitric oxide and prostacyclin formation), calcium antagonists inhibit the effects of vasoconstrictor hormones such as angiotensin II at the level of vascular smooth muscle by reducing calcium inflow and facilitating the vasodilator effects of nitric oxide. Calcium antagonists reduce smooth muscle cell proliferation and atherosclerosis. In hypertensive animals, verapamil and trandolapril normalize endothelial dysfunction. In large angiographic trials, nifedipine and nicardipine reduced the development of new atherosclerotic plaques. After myocardial infarction, verapamil reduces mortality and cardiac events in patients without heart failure. In contrast, ACE inhibitors are effective after myocardial infarction in patients with impaired left ventricular function. Urinary albumin excretion rate decreases during ACE inhibitor therapy or with a calcium antagonist such as verapamil; combination of the two drugs has an additive effect. In resistance arteries, hypertension is associated with an increased media/lumen ratio. ACE inhibitors, but not beta-blockers, markedly improve these structural changes. In summary, ACE inhibitors and calcium antagonists have a complementary profile, both in their hemodynamic and local vascular action. Hence, combination therapy with these two classes of drugs appears particularly useful in patients with hypertension, not only to lower blood pressure, but hopefully to achieve improved cardiovascular protection.
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PMID:Vascular protective effects of ACE inhibitors and calcium antagonists: theoretical basis for a combination therapy in hypertension and other cardiovascular diseases. 856 68

Left ventricular hypertrophy is well established as a blood pressure independent cardiovascular risk factor in patients on renal replacement therapy. The effects of antihypertensive treatment on myocardial structure and function in renal transplant recipients have been so far only rarely investigated. In a double-blind, placebo-controlled study patients were randomized to the calcium channel blocker nitrendipine or placebo if the transplanted kidney had developed a stable phase. Normotensive patients received nitrendipine 2 x 5 mg daily or placebo, hypertensive patients received 2 x 10 mg up to 2 x 20 mg nitrendipine daily or placebo. To achieve adequate blood pressure control, all patients with still elevated blood pressure on study medication received antihypertensive drugs other than calcium channels blockers. Ambulatory blood pressure recording and 2D-guided M-mode echocardiography were performed at baseline and upon completion of the study. In addition, laboratory workup (including serum creatinine and lipids) was done, and serum aldosterone, plasma renin activity, plasma angiotensin II and blood glucose levels were measured in all patients at baseline and after at least 12 months of therapy. Ambulatory blood pressure was almost identical between both groups at study baseline and follow-up. In renal transplant patients on nitrendipine, posterior wall thickness (-0.10 +/- 1.77 mm) and septal wall thickness (-0.83 +/- 2.23 mm) did not change significantly from baseline. In contrast, posterior wall thickness (0.71 +/- 0.92 mm, P < 0.01) and septal wall thickness (0.97 +/- 2.20 mm, P < 0.05) increased in patients on placebo, which differed from the observed changes on nitrendipine (ANOVA: P = 0.093 and P = 0.048, respectively). Relative wall thickness, a parameter for concentric left ventricular hypertrophy, became numerically smaller on nitrendipine therapy from 0.46 +/- 0.07 to 0.44 +/- 0.09 (-0.02 +/- 0.09, NS) but increased from 0.42 +/- 0.08 to 0.48 +/- 0.08 in the placebo arm (+0.04 +/- 0.08, P < 0.02), which was also significant between the two groups (ANOVA: P = 0.036). Endocrine parameters, lipids and blood glucose were not different between the two groups. We conclude from these data that the calcium channel blocker nitrendipine exerted beneficial effects on cardiac structure in patients after renal transplantation independent of blood pressure.
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PMID:Blood pressure independent effects of nitrendipine on cardiac structure in patients after renal transplantation. 943 Sep 2

Arterial hypertension (HBP) is a very important cardiovascular risk factor. According to the data from the Framingham Study, 90% of the patients with chronic heart failure (CHF) have a clinical history of HBP, and the risk of developing CHF is 2 to 3 times greater in hypertensive persons. Studies of general population by multivariate analysis have shown that HBP is responsible for 39% of CHF cases in males and 59% in females. On the other hand, there is a significant relation between HBP and coronary artery disease (CAD), another very important cause of CHF. HBP very frequently originates left ventricular hypertrophy (LVH) and this is one of the most important links between HBP, myocardium ischaemia, CAD, and sudden death from arrhythmias, to which it can lead. Recent studies on left ventricle systolic function in hypertensive patients indicate that about 1/6 of HBP patients with LVH present systolic dysfunction. Even more frequently, diastolic function is prematurely deteriorated in HBP. In spite of the existence of a significant relation between the grade of LVH and the severity of this disfunction, it may be present even before LVH is detectable. The transition from LVH would be related to quantitative and qualitative changes in the three compartments of the myocardium: hypertrophy of cardiomyocytes with reinduction of fetal genetic program, reactive and cicatricial fibrosis of the interstice, and functional and structural changes of coronary arteries. These modifications will progressively increase, leading to LV dilation which seems to signal transition to heart failure. In recent papers the transition from LVH to CHF has been related to a marked increase in microtubular intracytoplasmic structure, the reduction of Ca++ ATPase concentration of the sarcoplasmic reticulum, and the increased myocardial expression of growth factor TGF beta 1, which influences interstitial fibrosis. In the same way, stimulation of apoptosis by myocardial expression of tumor necrosis factor alpha and the subquent increase in inducible NO-synthase and oxidative stress has been related to the progression for CHF. Prevention of CHF will not only consist in the treatment of HBP but, very probably, also in the prevention of regression of LVH, and normalization of myocardial components, as well as the correction of all the factors involved in CHF establishment. In accordance with form of treatment, we must give special emphasis to drugs interfering with the renin-angiotensin system and, possibly in the near future, to gene therapy.
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PMID:[Hypertensive cardiopathy. From arterial hypertension to congestive heart failure]. 1042 61

The importance of the renin-angiotensin system (RAS) in blood pressure regulation is well established. High RAS activity has also been implicated in connection with elevated cardiovascular risk in patients with essential hypertension. Data from epidemiological studies have related high plasma renin levels in essential hypertensive patients to cardiovascular complications. However, whether renin itself is a risk factor of cardiovascular events or just acts as a marker for other risk factors still remains to be elucidated. Several possible mechanisms that could be responsible for the association between elevated RAS activity and cardiovascular risk are reviewed. The concept of high RAS activity being a cardiovascular risk factor is strongly supported by results from large clinical studies showing the beneficial effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in congestive heart failure and hypertension. Knowing more about the exact mechanisms of the association between high RAS activity and cardiovascular complications would enable us to profile the treatment of high blood pressure more specifically to improve outcome in individuals or groups of patients.
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PMID:The renin-angiotensin system in essential hypertension: associations with cardiovascular risk. 1045 Oct 33

Left ventricular hypertrophy (LVH) has been recognized as an important cardiovascular risk factor. Hypertensive disease is the most frequent background of LVH and it is generally felt that anti-hypertensive treatment should not only lower blood pressure but also cause regression of LVH. In the present survey the patho-physiology of LVH, its measurements and animal models used to study LVH are briefly discussed. Subsequently, the effects of various drugs in animal models and in human hypertensives are reviewed. It has been shown repeatedly that various types of antihypertensive drugs show differential activities on the prevention or regression of LVH. It is not only the lowering of blood pressure which determines the anti-LVH activity, but also the interaction of drugs with neuro-endocrine mechanisms such as the renin-angiotensin-aldosterone system and the sympathetic nervous system.
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PMID:The influence of antihypertensive drug treatment on the prevention and regression of left ventricular hypertrophy. 1072 16

Obese hypertensive patients with cardiovascular risk factor clustering and increased risk for atherosclerotic disease have increased plasma nonesterified fatty acid levels, including oleic acid (OA), and a more active renin-angiotensin-aldosterone system. Vascular smooth muscle cell (VSMC) migration and proliferation participate in the development of atherosclerotic plaque. OA and angiotensin (Ang) II induce synergistic mitogenic responses in VSMCs through sequential signaling pathways dependent on the activation of protein kinase C (PKC), oxidants (reactive oxygen species, ROS), and extracellular signal-regulated kinase (ERK) activation. We tested the hypotheses that (1) OA and Ang II have additive or synergistic effects on VSMC migration and (2) PKC, ROS, and mitogen-activated protein kinase are critical signaling molecules. OA at 100 micromol/L increases VSMC migration 60+/-10% over control (P:<0.001). Ang II (10(-)(9) mol/L) increases VSMC migration by 62+/-13% and 73% over control, respectively (P:<0.01). Coincubation of cells with OA and Ang II produces a nearly additive increase in VSMC cell migration at 107+/-20% (P:<0.01). Increases in VSMC migration induced by OA alone and combined with Ang II were reduced by PKC inhibition and downregulation. VSMC migration in response to OA alone and with Ang II was also inhibited by N:-acetyl-cysteine, MEK inhibition, and ERK antisense. VSMC migration in response to OA alone or combined with Ang II is dependent on activation of PKC, ROS, and ERK activation, further raising the possibility that increased plasma nonesterified fatty acids and an activated renin-angiotensin-aldosterone system in subjects with the risk factor cluster contribute to accelerated atherosclerosis through a PKC, ROS, and ERK-dependent signaling pathway.
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PMID:Signaling events mediating the additive effects of oleic acid and angiotensin II on vascular smooth muscle cell migration. 1123 Feb 90

The Reduction in End Points in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study and the Irbesartan Diabetic Nephropathy Trial (IDNT) are two recently reported trials with hard end points, conducted in patients in advanced stages of diabetic nephropathy. Two other studies--the Irbesartan Microalbuminuria Study (IRMA)-2 and the Microalbuminuria Reduction with Valsartan study (MARVAL)--were trials conducted in patients with type 2 diabetes with microalbuminuria, a cardiovascular risk factor associated with early-stage diabetic nephropathy. These trials all had a common theme--that is, does an angiotensin receptor blocker (ARB) interfere with the natural history of diabetic nephropathy in a blood pressure-independent fashion? Without question, the results of these trials legitimatize the use of the ARB class in forestalling the deterioration in renal function, which is almost inevitable in the patient with untreated diabetic nephropathy. These data can now be added to the vast array of evidence supporting angiotensin-converting enzyme (ACE) inhibitor use in patients with nephropathy associated with type 1 diabetes. It now appears a safe conclusion that the patient with diabetic nephropathy should receive therapy with an agent that interrupts the renin-angiotensin system. These studies have not resolved the question as to whether an ACE inhibitor or an ARB is the preferred agent in people with nephropathy from type 1 diabetes, though the optimal doses of these drugs remain to be determined. Head-to-head studies comparing ACE inhibitors to ARBs in diabetic nephropathy are not likely to occur, so it is unlikely that comparable information will be forthcoming with ACE inhibitors. An evidence-based therapeutic approach derived from these trials would argue for ARBs to be the foundation of therapy in the patient with type 2 diabetes and nephropathy.
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PMID:Type 2 diabetes: RENAAL and IDNT--the emergence of new treatment options. 1182 41

Left ventricular hypertrophy (LVH) is a major cardiovascular risk factor for morbidity and mortality. It is caused by arterial hypertension, although various hemodynamic and nonhemodynamic factors contribute to its development. Especially, the renin-angiotensin-aldosterone system is involved in the pathophysiology of LVH. The Treatment of Mild Hypertension study demonstrated that in mild essential hypertension, nonpharmacologic treatment is an effective tool for treating LVH. There are at least three major meta-analyses with several thousand patients examining the ability of antihypertensive drugs on the reversal of LVH. The results of these meta-analyses are very consistent. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers achieve significantly better results than b-blockers. The most recently published Losartan Intervention For Endpoint reduction in hypertension study confirmed the superiority of angiotensin receptor blockers against b-blockers in a large-scale prospective trial. It also proves for the first time that regression of LVH is associated with better cardiovascular outcome.
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PMID:Are all antihypertensive drug classes equal in reducing left ventricular hypertrophy? 1237 66


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