Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Guidelines originally were published in 2002 based on best available scientific data as well as consensus of expert opinion in the absence of controlled clinical trial data to assist ophthalmologists with selection of patients for whom photodynamic therapy with verteporfin (Visudyne, Novartis AG, Basel, Switzerland), termed "verteporfin therapy," should be considered, and to offer suggestions regarding initial treatment, follow-up, and additional courses of treatment at follow-up. Consensus was based on results of clinical trials and expert opinion. Additional input and advice were received from representatives on behalf of the American Society of Retina Specialists, the Macula Society, and the Retina Society, as well as principal investigators of randomized clinical trials evaluating verteporfin therapy. Since 2002, additional information relevant to clinical care was published in the peer-reviewed literature; therefore, revisions to the originally published guidelines judged warranted are provided here. Patient selection criteria include the following: (1) in cases due to age-related macular degeneration (AMD), lesion composition of (a) predominantly classic choroidal neovascularization (CNV), (b) occult with no classic CNV with presumed recent disease progression, or (c) relatively small minimally classic lesions; (2) CNV location subfoveal or so close to the foveal center that conventional laser photocoagulation treatment almost certainly would extend under the center; (3) etiology of CNV from AMD, pathologic myopia, or other causes in which the outcome without treatment is likely to be worse than with treatment; and (4) vision at a level where further loss would be recognized as detrimental to the quality of life of the patient. Criteria include lesion size for AMD patients with either a minimally classic lesion composition (where treatment usually should be considered only for relatively smaller lesions) or occult with no classic lesions (where treatment usually should be considered for relatively smaller lesions or those >4 Macular Photocoagulation Study disc areas with a relatively lower or poorer best-corrected visual acuity) but not patient age, history of systemic arterial hypertension, or prior laser photocoagulation. Therapy should be initiated ideally within 1 week of the initial fluorescein angiogram on which the clinical decision to treat is based. Patients should return for follow-up at least as often as every 3 months (+/-2 weeks) after any initial or subsequent treatment to determine if there is fluorescein leakage from CNV. Additional courses of treatment should be considered as often as every 3 months (+/-2 weeks) if fluorescein leakage from CNV is noted at that time. Additional courses of treatment could be deferred if the biomicroscopic and fluorescein angiographic appearances of the lesion are unchanged and show minimal fluorescein leakage, especially when there is no subretinal fluid or fluorescein leakage from CNV underlying the center of the foveal avascular zone. Patients should avoid exposure of skin or eyes to direct sunlight or bright indoor light for 48 hours after treatment or until resolution of any swelling or discoloration from extravasation. Follow-up of relatively larger minimally classic lesions and occult with no classic lesions that initially do not undergo therapy appears indicated so therapy can be considered if a predominantly classic lesion develops or, in the case of occult with no classic lesions, if visual acuity declines slightly to a lower (poorer) level without a marked increase in lesion size. Additional revisions of these guidelines may be required as new data become available.
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PMID:Guidelines for using verteporfin (Visudyne) in photodynamic therapy for choroidal neovascularization due to age-related macular degeneration and other causes: update. 1568

Macula densa (MD) cells of the juxtaglomerular apparatus (JGA) synthesize type 1 nitric oxide synthase (NOS1) and type 2 cyclooxygenase (COX-2). Both nitric oxide (NO) and prostaglandins have been considered to mediate or modulate the control of renin secretion. Reactive oxygen species (ROS) produced locally by NADPH oxidase may influence NO bioavailability. We have tested the hypothesis that in hypertension elevated ROS levels may modify the expression of NOS1 and COX-2 in the JGA, thereby interacting with juxtaglomerular signaling. To this end, spontaneously hypertensive rats (SHR) and Wistar-Kyoto control rats (WKY) received the specific NADPH oxidase inhibitor, apocynin, during 3 wk. Renal functional and histochemical parameters, plasma renin activity (PRA), and as a measure of ROS activity, urinary isoprostane excretion (IP) were evaluated. Compared with WKY, IP levels in untreated SHR were 2.2-fold increased, and NOS1 immunoreactiviy (IR) of JGA 1.5-fold increased, whereas COX-2 IR was reduced to 35%, renin IR to 51%, and PRA to 7%. Apocynin treatment reduced IP levels in SHR to 52%, NOS1 IR to 69%, and renin IR to 62% of untreated SHR, whereas renin mRNA, COX-2 IR, glomerular filtration rate, PRA, and systolic blood pressure remained unchanged. WKY revealed no changes under apocynin treatment. These data show that NADPH oxidase is an important contributor to elevated levels of ROS in hypertension. Upregulation of MD NOS1 in SHR may have the potential of blunting the functional impact of ROS at the level of bioavailable NO. Downregulated COX-2 and renin levels in SHR are apparently unrelated to oxidative stress, since apocynin treatment had no effect on these parameters.
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PMID:Effect of apocynin treatment on renal expression of COX-2, NOS1, and renin in Wistar-Kyoto and spontaneously hypertensive rats. 1646 5

Macula densa cells have an important role in the regulation of glomerular blood flow and glomerular filtration by its regulation of afferent arteriolar vascular tone. Nitric oxide derived from neuronal nitric oxide synthase (nNOS) in macula densa can dilate afferent arterioles. Macula densa nNOS is important for renin secretion, and its expression is regulated by dietary salt, renal angiotensin II, intracellular pH, and other factors. In salt-sensitive hypertension, nNOS is suppressed, whereas in SHR or in the early phase of diabetes, nNOS is increased in macula densa along with NADPH oxidase, which limits NO bioavailability. Renal damage induced by hypertension, diabetes, and hyperlipidemia could be prevented by enhancement of nNOS in macula densa with ACEI, dipyridamole, alpha(1)-receptor blocker, a low-salt diet, or sodium bicarbonate. Sodium bicarbonate is a safe and clinically available enhancer of nNOS in macula densa that increases glomerular blood flow and prevents the reduction of GFR in radiocontrast nephropathy and chronic renal failure. In conclusion, the enhancement of nNOS in the macula densa can be a promising strategy to prevent reduction of renal function.
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PMID:Role of macula densa neuronal nitric oxide synthase in renal diseases. 1657 7

Macula densa cells produce superoxide (O2-) during tubuloglomerular feedback primarily via NAD(P)H oxidase (NOX). The purpose of the present study was to determine NOXs expressed by the macula densa and the role of each one in NaCl-induced O2- production. To identify which isoforms are expressed, we applied single-cell RT-PCR to macula densa cells isolated by laser capture microdissection and to MMDD1 cells (a macula densa-like cell line). The captured cells expressed neuronal NOS (marker of macula densa), NOX2, and NOX4 but not NOX1. Expression of the NOXs and neuronal NOS was essentially identical in the MMDD1 cells. Thus, we used MMDD1 cells to investigate which isoform is responsible for NaCl-induced O2- production. We used small-interfering RNA to knock down NOX2 or NOX4 in MMDD1 cells and measured O2- exposed to low-salt solution (LS; 70 mmol/L of NaCl) or high-salt solution (HS; 140 mmol/L of NaCl). Exposing control cells (scrambled small-interfering RNA) to HS increased O2- concentrations from 0.75+/-0.28 to 1.48+/-0.46 U/min per 10(5) cells in LS and HS, respectively (P<0.001). Inhibiting NOX2 blocked the HS-induced increase in O2- (0.62+/-0.39 versus 0.76+/-0.31 U/min per 10(5) cells in LS and HS groups, respectively). Blocking NOX4 did not affect HS-induced O2- levels. O2- levels in the control cells during LS and HS were 0.80+/-0.30 and 1.56+/-0.49 U/min per 10(5) cells, respectively (P<0.001); whereas O2- levels in NOX4-small-interfering RNA-treated cells during LS and HS were 0.40+/-0.25 and 1.26+/-0.51 U/min per 10(5) cells, respectively (P<0.001). We conclude that, whereas macula densa cells express the NOX2 and NOX4 isoforms, NOX2 is primarily responsible for NaCl-induced O2- generation.
Hypertension 2009 Mar
PMID:Isoforms and functions of NAD(P)H oxidase at the macula densa. 1920 81