Biomedical subjects

Nancy J Brown

Publications and source records attributed to Nancy J Brown.

51 records · Page 3Linked to original sources

PubMed2003

Characterization of the CYP4A11 gene, a second CYP4A gene in humans.

Comparison between the cDNA sequence of CYP4A11 and that deduced from a published genomic clone suggested the presence of an additional CYP4A gene in humans, CYP4A22. PCR amplification of genomic DNA yielded overlapping clones covering 13kb of genomic DNA and extending from 1003bp upstream from CYP4A11 translation initiation to 135bp upstream of the mRNA polyadenylation signal. Sequence and Southern blot analysis showed the presence in humans of two highly homologous CYP4A genes, CYP4A11 and CYP4A22. These two genes share 96% sequence identity and have similar intron/exon sizes and distribution. Short nucleotide insertions (< or =10bp) in introns 1, 3, 9, and 11, and deletions (< or =18bp) in introns 4, 6, and 11 differentiate the two genes. RT-PCR amplification of human kidney RNA followed by restriction fragment analysis showed that CYP4A11 is the predominant isoform expressed in kidney.

Base Sequence↗

PubMed2003

Effect of combined AT1 receptor and aldosterone receptor antagonism on plasminogen activator inhibitor-1.

Aldosterone enhances angiotensin II (Ang II)-induced plasminogen activator inhibitor (PAI)-1 expression in vitro. This study tested the hypothesis that angiotensin II type 1 (AT(1)) and aldosterone receptor antagonism interact to decrease PAI-1 in humans. Effects of candesartan (16 mg/d), spironolactone (25 mg/d), or combined candesartan/spironolactone on mean arterial pressure (MAP), endocrine, and fibrinolytic variables were measured in 18 normotensive subjects [age 33.7 yr (95% confidence interval 29.3, 38.0), body mass index 26.6 (24.7, 28.4) kg/m(2)] in whom the renin-angiotensin-aldosterone system was activated by furosemide (20 mg/d). Candesartan [83.3 mm Hg (78.9, 87.7)], but not spironolactone [89.4 mm Hg (85.4, 93.5)], decreased MAP, compared with baseline [92.2 mm Hg (88.9, 95.5), P < 0.001] and furosemide alone [89.1 mm Hg (85.7, 92.4), P = 0.002]. Coadministration of spironolactone with candesartan did not further decrease MAP. Candesartan dramatically increased Ang II [177.9 pg/ml (113.3, 242.6)], compared with baseline [34.8 pg/ml (29.3, 40.4), P = 0.002] and furosemide alone [40.6 pg/ml (29.7, 51.5), P = 0.003]. Spironolactone increased Ang II [51.5 pg/ml (41.3, 61.7), P = 0.014 vs. baseline, P = 0.004 vs. candesartan]. There was no additive effect of candesartan and spironolactone on Ang II [197.6 pg/ml (134.2, 261.0)]. Aldosterone was lower during candesartan [8.9 ng/dl (7.3, 10.6), P = 0.007] than during furosemide alone [14.1 ng/dl (10.9, 17.3), P = 0.007], spironolactone [18.7 ng/dl (14.5, 22.9), P = 0.002], or combined candesartan/spironolactone [13.9 ng/dl (11.8, 15.9), P = 0.006]. Furosemide increased PAI-1 antigen [27.8 ng/ml (20.6, 35.0), P = 0.002 vs. 19.3 ng/ml (13.4, 25.2) baseline], even in the presence of candesartan [27.2 ng/ml (16.5, 37.8), P = 0.042 vs. baseline] or spironolactone [27.3 ng/ml (17.9, 36.8), P = 0.015 vs. baseline]. However, coadministration of AT(1) and aldosterone receptor antagonists prevented the furosemide-induced increase in PAI-1 [19.2 ng/ml (9.8, 28.6), P = 0.974 vs. baseline, P < 0.05 vs. candesartan, spironolactone or furosemide alone]. This study evidences an interactive effect of endogenous Ang II and aldosterone on PAI-1 production in humans.

Adult↗

PubMed2002

Ethnicity affects vasodilation, but not endothelial tissue plasminogen activator release, in response to bradykinin.

Previous studies indicate that the vasodilator response to bradykinin (BK) and other endothelium-dependent and -independent agonists is decreased in black Americans compared with white Americans. The purpose of the present study was to determine the effect of ethnicity on fibrinolytic function in humans. Graded doses of BK (100, 200, and 400 ng/min), acetylcholine (15, 30, and 60 microg/min; N=20), or methacholine (3.2, 6.4, 12.8 microg/min; N=20), and sodium nitroprusside (0.8, 1.6, and 3.2 microg/min) were infused via brachial artery in 19 white and 21 black age-matched normotensive subjects. Forearm blood flow (FBF) was measured by plethysmography, and venous and arterial samples were collected for tissue plasminogen activator (tPA) antigen. Compared with whites (increase in FBF from 3.7+/-0.5 to 23.9+/-2.5 mL x min(-1) x 100 mL(-1)), blacks (increase in FBF from 2.8+/-0.3 to 15.2+/-1.9 mL x 100 mL(-1) x min(-1)) exhibited a blunted FBF response to BK (P=0.035). Responses to sodium nitroprusside and methacholine or acetylcholine were similarly decreased. In contrast, there was no effect of ethnicity on net tPA antigen release in response to BK (increase from -0.2+/-0.4 to 67.3+/-15.2 ng x min(-1) x 100 mL(-1) in blacks; from 0.04+/-0.9 to 65.9+/-13.6 ng x min(-1) x 100 mL(-1) in whites). Thus, ethnicity significantly influenced the relationship between the flow and tPA release responses to BK (P=0.037). These data suggest that the BK-dependent alterations in vascular fibrinolytic function are preserved in black Americans compared with white Americans.

Adult↗

PubMed2002

G protein-coupled receptor kinase 4 gene variants in human essential hypertension.

Essential hypertension has a heritability as high as 30-50%, but its genetic cause(s) has not been determined despite intensive investigation. The renal dopaminergic system exerts a pivotal role in maintaining fluid and electrolyte balance and participates in the pathogenesis of genetic hypertension. In genetic hypertension, the ability of dopamine and D(1)-like agonists to increase urinary sodium excretion is impaired. A defective coupling between the D(1) dopamine receptor and the G protein/effector enzyme complex in the proximal tubule of the kidney is the cause of the impaired renal dopaminergic action in genetic rodent and human essential hypertension. We now report that, in human essential hypertension, single nucleotide polymorphisms of a G protein-coupled receptor kinase, GRK4gamma, increase G protein-coupled receptor kinase (GRK) activity and cause the serine phosphorylation and uncoupling of the D(1) receptor from its G protein/effector enzyme complex in the renal proximal tubule and in transfected Chinese hamster ovary cells. Moreover, expressing GRK4gammaA142V but not the wild-type gene in transgenic mice produces hypertension and impairs the diuretic and natriuretic but not the hypotensive effects of D(1)-like agonist stimulation. These findings provide a mechanism for the D(1) receptor coupling defect in the kidney and may explain the inability of the kidney to properly excrete sodium in genetic hypertension.

Animals↗

PubMed2002

Smoking impairs bradykinin-stimulated t-PA release.

Bradykinin stimulates tissue plasminogen activator release from human endothelium through a flow-independent, B2 receptor-dependent mechanism. The present study tests the hypothesis that smoking impairs bradykinin-stimulated tissue plasminogen activator release. Graded doses of nitroprusside (1.6 to 6.4 microg/min), methacholine (3.2 to 12.8 microg/min), and bradykinin (100 to 400 ng/min) were infused in the brachial artery in random order in 20 smokers and 12 nonsmokers matched for age, gender, and body mass index. Forearm blood flow was measured by strain-gauge plethysmography. All 3 drugs caused a dose-dependent increase in forearm blood flow, with no significant difference between smokers and nonsmokers. Bradykinin (P=0.001) and methacholine (P=0.001) caused significant dose-dependent increases in net tissue plasminogen activator release. The tissue plasminogen activator response to bradykinin was significantly greater than the tissue plasminogen activator response to methacholine in the nonsmokers (maximal net tissue plasminogen activator release, 73.2+/-21.5 versus 27.6+/-7.2 ng/min per 100 mL; P=0.001) but not in the smokers (maximal net tissue plasminogen activator release, 44.5+/-10.7 versus 24.8+/-9.3 ng/min per 100 mL; P=0.154). The effect of bradykinin (P=0.037), but not methacholine (P=0.978), on net tissue plasminogen activator release was significantly reduced in smokers compared with nonsmokers. The vascular tissue plasminogen activator response to bradykinin, but not methacholine, is impaired in smokers. Stimulated tissue plasminogen activator release may be a more sensitive measure of endothelial function than vasodilation.

Adult↗

PubMed2002

Comparative effects of estrogen and angiotensin-converting enzyme inhibition on plasminogen activator inhibitor-1 in healthy postmenopausal women.

BACKGROUND: This study compares the effect of estrogens and ACE inhibition on plasminogen activator inhibitor-1 (PAI-1) concentrations in healthy postmenopausal women, genotyped for a 4G/5G polymorphism in the PAI-1 promoter, a polymorphism shown to influence PAI-1 concentrations. Methods and Results- Morning estradiol, PAI-1, tissue plasminogen activator, plasma renin activity, angiotensin II, and aldosterone were measured in 19 postmenopausal women (5G/5G:4G/5G:4G4G=5:10:4, respectively) at baseline and during randomized, single-blind, crossover treatment with conjugated equine estrogens 0.625 mg per os per day, ramipril 10 mg per os per day, and combination estrogens and ramipril. Estradiol (P<0.005) and angiotensin II (P<0.01) were significantly higher during estrogens. Plasma renin activity was significantly increased during ACE inhibition (P<0.05). Both conjugated estrogens [PAI-1 antigen from 12.5 (7.6, 17.4) [mean (95% CI)] baseline to 6.6 (2.6, 10.7) ng/mL, P<0.01] and ACE inhibition [8.3 (4.9, 11.7) ng/mL, P<0.005] decreased PAI-1 without decreasing tissue plasminogen activator. The effect of combined therapy on PAI-1 [5.6 (2.3, 8.8) ng/mL] was significantly greater than that of ramipril alone (P<0.05). There was a significant effect of PAI-1 4G/5G genotype on baseline PAI-1 concentrations (P=0.001) and a significant interactive effect of 4G/5G genotype and treatment, such that genotype influenced the change in PAI-1 during ramipril (P=0.011) or combined therapy (P=0.006) but not during estrogens (P=0.715). CONCLUSIONS: ACE inhibition with ramipril and conjugated estrogens similarly decrease PAI-1 antigen concentrations in postmenopausal women. Larger studies that use clinical outcomes are needed to determine whether PAI-1 4G/5G genotype should influence the choice of conjugated estrogens or ACE inhibition for the treatment of healthy postmenopausal women.

Aldosterone↗

PubMed2002

Potential roles of plasminogen activator system in coronary vascular remodeling induced by long-term nitric oxide synthase inhibition.

Recent studies have indicated that a number of factors contribute to the pathophysiology in response to nitric oxide synthase (NOS) inhibition. We previously demonstrated that plasminogen activator inhibitor-1 deficient (PAI-1-/-) mice are protected against hypertension and perivascular fibrosis induced by relatively short-term NOS inhibition. In this study, we compared the temporal changes in systolic blood pressure and coronary perivascular fibrosis induced by long-term treatment with N(omega)-nitro- L -arginine methyl ester (L -NAME) in wild type (WT), PAI-1(-/-) and tissue-type plasminogen activator deficient (t-PA-/-) mice. After initiating L -NAME, systolic blood pressure increased in all groups at 2 weeks. Over a 16 week study period, systolic blood pressure increased to 143+/-3 mmHg (mean+/-SEM) in WT animals, 139+/-2 in t-PA-/- mice vs 129+/-2 in PAI-1-/- mice (P < 0.01). Coronary perivascular fibrosis increased in L -NAME-treated WT and t-PA(-/-) mice compared to each control group (P<0.01 in WT, P<0.05 in t-PA-/-), while PAI-1-/- mice were protected against fibrosis induced by L -NAME. t-PA deficiency did not accentuate the vascular pathology or the changes in blood pressure. In situ zymography demonstrated augmented gelatinolytic activity in PAI-1-/- mice at baseline, suggesting that PAI-1 deficiency prevents the increase of collagen deposition by promoting matrix degradation. Plasma TGF-beta1 levels increased in L -NAME-treated WT and PAI-1-/- mice (P < 0.01), but not in L -NAME-treated t-PA-/- mice. These findings support the hypothesis that the plasminogen activator system protects against the structural vascular changes induced by long-term NOS inhibition. While PAI-1 deficiency protects against L -NAME-induced hypertension and perivascular fibrosis, t-PA deficiency does not exacerbate the vascular pathology or hypertension.

Animals↗

PubMed2002

PAI-1 in human hypertension: relation to hypertensive groups.

BACKGROUND: Although the renin-angiotensin system and insulin resistance (IR) have been identified as major regulators of plasminogen activator inhibitor type-1 (PAI-1), their roles in hypertensive subjects is not clearly defined. METHODS: We examined the effect of dietary salt restriction on PAI-1 levels in 239 hypertensive subjects from three centers. Subjects were placed on a 200 and 10 mmol/day sodium diets for 1-week periods. Plasma renin activity (PRA) and PAI-1 levels were measured on the last day of both diets and fasting insulin, glucose, and aldosterone (ALDO) levels, only on the low salt diet. RESULTS: Sodium restriction increased PAI-1 levels from 32.1 +/- 2.5 ng/mL to 39.8 +/- 3.2 ng/mL (P = .009). There was a strong positive correlation between PAI-1 levels and PRA (r = 0.228, P = .0004), IR (r = 0.222, P = .001), triglycerides (r = 0.275, P < .001), and ALDO (P = .018 for linear trend). The patients were divided into low renin (low IR and ALDO levels), nonmodulators (normal PRA, high IR, and low ALDO levels), and modulators (normal PRA, intermediate IR, and normal ALDO levels) groups to assess the relative contribution of each factor to PAI-1 levels. Modulators had significantly (P = .019) higher PAI-1 levels compared to the low renin and nonmodulators who had similar PAI-1 levels. CONCLUSIONS: Plasma renin activity, IR, and ALDO all correlate with PAI-1 levels in the hypertensive subjects. However, the data suggest that ALDO may be an important factor contributing to the variability of PAI-1 levels in individual hypertensive subjects.

Adult↗

PubMed2002

Improving medication use in newly admitted home healthcare patients: a randomized controlled trial.

OBJECTIVES: To test the efficacy of a medication use improvement program developed specifically for home health agencies. The program addressed four medication problems identified by an expert panel: unnecessary therapeutic duplication, cardiovascular medication problems, use of psychotropic drugs in patients with possible adverse psychomotor or adrenergic effects, and use of nonsteroidal antiinflammatory drugs (NSAIDs) in patients at high risk of peptic ulcer complications. It used a structured collaboration between a specially trained clinical pharmacist and the patients' home-care nurses to improve medication use. DESIGN: Parallel-group, randomized controlled trial. SETTING: Two of the largest home health agencies in the United States. PARTICIPANTS: Study subjects were consenting Medicare patients aged 65 and older admitted to participating agency offices from October 1996 through September 1998, with a projected home healthcare duration of at least 4 weeks and at least one study medication problem. INTERVENTION: Qualifying patients were randomized to usual care or usual care with the medication improvement program. MEASUREMENTS: Medication use was measured during an in-home interview, with container inspection at baseline and at follow-up (between 6 and 12 weeks) by interviewers unaware of treatment assignment. The trial endpoint was the proportion of patients with medication use improvement according to predefined criteria at follow-up. RESULTS: There were 259 randomized patients with completed follow-up interviews: 130 in the intervention group and 129 with usual care. Medication use improved for 50% of intervention patients and 38% of control patients, an attributable improvement of 12 patients per 100 (95% confidence interval (CI) = 0.0-24.0, P =.051). The intervention effect was greatest for therapeutic duplication, with improvement for 71% of intervention and 24% of control patients, an attributable improvement of 47 patients per 100 (95% CI = 20-74, P =.003). Use of cardiovascular medications also improved more frequently in intervention patients: 55% vs 18%, attributable improvement 37 patients per 100 (95% CI = 9-66, P =.017). There were no significant improvements for the psychotropic medication or NSAID problems. There was no evidence of adverse intervention effects: new medication problems, more agency nurse visits, or increased duration of home health care. CONCLUSIONS: A program congruent with existing personnel and practices of home health agencies improved medication use in a vulnerable population and was particularly effective in reducing therapeutic duplication.

Aged↗

PubMed2002

The renin-angiotensin-aldosterone system and fibrinolysis in progressive renal disease.

Renal glomerular and interstitial fibrosis is widely viewed as the final common pathway to renal failure, regardless of the initiating injury. Similarly, the renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of renal disease. This review explores the hypothesis that the RAAS causes injury and fibrosis, in part, through effects on plasminogen activator inhibitor-1 (PAI-1), the major physiologic inhibitor of plasminogen activators in vivo. PAI-1, by inhibiting the production of plasmin from plasminogen, tips the balance in favor of extracellular matrix accumulation and promotes fibrosis. Interruption of the RAAS decreases both PAI-1 expression and fibrosis in animal models. These findings have implications for the clinical management of renal disease.

Disease Progression↗

PubMed2002

ACE inhibition versus angiotensin type 1 receptor antagonism: differential effects on PAI-1 over time.

ACE inhibition reduces plasminogen activator inhibitor-1 (PAI-1), a risk factor for myocardial infarction, whereas the effect of angiotensin receptor antagonism on PAI-1 is uncertain. The present study compares the time course of effects of ACE inhibition and angiotensin type 1 (AT1) receptor antagonism on morning plasma PAI-1 antigen. Blood pressure and endocrine, metabolic, and fibrinolytic variables were measured in 20 insulin-resistant (defined by fasting glucose >8.3 mmol/L, body mass index >28 kg/m2, or fasting serum triglyceride > or =2.8 mmol/L) hypertensive subjects (mean age, 47.9+/-2.1 years) (1) before and after 1 week of hydrochlorothiazide 12.5 mg/d, and (2) before and 1, 3, 4, and 6 weeks after addition of ramipril (escalated to 10 mg/d) or losartan (escalated to 100 mg/d). Hydrochlorothiazide decreased systolic (P=0.011) and diastolic (P=0.019) pressure. Ramipril (from 133.6+/-5.1/94.5+/-2.4 to 127.0+/-3.1/91.4+/-3.3 mm Hg) or losartan (from 137.0+/-3.9/93.1+/-2.9 to 123.7+/-2.6/86.4+/-2.1 mm Hg) further reduced systolic (P=0.009) and diastolic (P=0.037) pressure. The pressure effects of the 2 drugs were similar. Hydrochlorothiazide increased plasma PAI-1 (P=0.013) but not tissue-type plasminogen activator (tPA) (P=0.431) antigen. Addition of either ramipril or losartan significantly decreased plasma PAI-1 antigen (P=0.046). However, the effect of losartan on PAI-1 antigen was not sustained throughout the 6-week treatment period, such that there was a significant drugxtime interaction (P=0.043). tPA antigen decreased during either ramipril or losartan (P=0.032), but tPA activity decreased only during losartan (P=0.018). Short-term interruption of the renin-angiotensin-aldosterone system by either ACE inhibition or AT1 receptor antagonism decreases PAI-1 antigen, but the duration of this effect is greater for ACE inhibition than for AT1 receptor antagonism.

Angiotensin Receptor Antagonists↗

PubMed2002

Dipeptidyl peptidase IV activity in patients with ACE-inhibitor-associated angioedema.

Bradykinin and substance P have been implicated as mediators in angiotensin-converting enzyme inhibitor (ACEI)-associated angioedema. Studies investigating the metabolism of bradykinin in sera from patients with a history of ACEI-associated angioedema and controls suggest that there is a defect in a non-ACE, non-kininase I pathway of bradykinin degradation, such as the aminopeptidase P (APP)/dipeptidyl peptidase IV (DPPIV) pathway. This study tested the hypothesis that serum APP or DPPIV activity is decreased in patients with ACEI-associated angioedema. APP and DPPIV activity were measured in sera collected from patients during ACEI-associated angioedema, from patients with a remote history of ACEI-associated angioedema, and from normotensive and untreated hypertensive controls. The effects of acute and chronic ACEI and corticosteroid treatment on serum DPPIV activity were also assessed. DPPIV activity was similar in normotensive volunteers (37.8 +/- 6.3 nmol/mL per min), in untreated hypertensive subjects who had been exposed previously to ACEI without angioedema (36.2 +/- 4.3 nmol/mL per min), in hypertensive patients with a remote history of angioedema (35.1 +/-8.5 nmol/mL per min), and in chronically ACEI-treated hypertensive subjects (36.1 +/- 5.6 nmol/mL per min). DPPIV activity decreased with increasing age (R(2)=0.10, P=0.016). Subject group significantly affected DPPIV activity (F=6.208, P=0.016) such that DPPIV activity was significantly lower in patients with ACEI-associated angioedema (26.9 +/- 4.1 nmol/mL per min) than in normotensive controls, in previously ACEI-exposed untreated hypertensive volunteers, or in ACEI-treated hypertensive volunteers, even after controlling for age. There was no effect of acute ACE inhibition or corticosteroids on DPPIV activity. With respect to APP activity, there was no difference between groups. These results suggest that DPPIV activity is depressed in individuals with hypertension during acute ACEI-associated angioedema.

Adult↗

PubMed2002

Spironolactone abolishes the relationship between aldosterone and plasminogen activator inhibitor-1 in humans.

Recent studies have defined a link between the renin-angiotensin-aldosterone system and fibrinolysis. The present study tests the hypothesis that endogenous aldosterone regulates plasminogen activator inhibitor-1 (PAI-1) production in humans. Hemodynamic parameters, PAI-1 and tissue-type plasminogen activator (t-PA) antigen, potassium, PRA, angiotensin II, and aldosterone were measured in nine male hypertensive subjects after a 3-wk washout, after 2 wk of hydrochlorothiazide (HCTZ; 25 mg plus 20 mmol KCl/d), and after 2 wk of spironolactone (100 mg/d plus KCl placebo). Spironolactone (P = 0.04), but not HCTZ (P = 0.57 vs. baseline; P = 0.1 vs. spironolactone), significantly lowered systolic blood pressure. Angiotensin II increased from baseline during both HCTZ (P = 0.02) and spironolactone (P = 0.02 vs. baseline; P = 0.19 vs. HCTZ) treatments. Although both HCTZ (P = 0.004) and spironolactone (P < 0.001 vs. baseline) increased aldosterone, the effect was greater with spironolactone (P < 0.001 vs. HCTZ). HCTZ increased PAI-1 antigen (P = 0.02), but did not alter t-PA antigen. In contrast, there was no effect of spironolactone on PAI-1 antigen (P = 0.28), whereas t-PA antigen was increased (P = 0.01). There was a significant correlation between PAI-1 antigen and serum aldosterone during both baseline and HCTZ study days (r(2) = 0.57; P = 0.0003); however, treatment with spironolactone abolished this correlation (r(2) = 0.13; P = 0.33). This study provides evidence that endogenous aldosterone influences PAI-1 production in humans.

Adult↗

PubMedDate not supplied

Assessment of community contamination: a critical approach.

The purpose of this paper is to review data from two Superfund sites and describe the latitude of interpretation of "environmental risk" by residents living in the area, governmental agencies, and the media. The first community was located within a 5-mi perimeter of the Rocky Flats Environmental Technology Site (RFETS) outside Denver, Colorado. The second community was located on the south side of Tucson, Arizona, adjacent to the Tucson International Airport area (TIAA) Superfund site. Critical theory was the perspective used in this analysis and proposal of public health actions to attain social justice. Differences between the two populations' experiences with risk and contamination coincided with divergent levels of trust in government. RFETS residents demanded monitoring, whereas the minority residents at TIAA were ambivalent about their trust in government cleanup activities. Unraveling the purpose of "facts" and the social force of "truth" can direct nurses to address environmental justice issues. By policing governmental and business activities in halting or cleaning up environmental contamination, nurses may become mouthpieces for the concerns underlying the fragile surface of "virtual trust" in contaminated communities. Cutting through competing rhetoric to police environmental safety, the core function of assurance becomes what nurses do, not what they say.

Arizona↗

PubMedDate not supplied

Aldosterone and PAI-1: implications for renal injury.

Aldosterone modulates cardiovascular and renal injury and fibrosis in animal models. This review explores the hypothesis that aldosterone causes injury and fibrosis, in part, through effects on plasminogen activator inhibitor-1, the major physiological inhibitor of plasminogen activators in vivo. Aldosterone interacts with angiotensin II to increase plasminogen activator inhibitor-1 expression in vitro and in vivo. Plasminogen activator inhibitor-1, by inhibiting the production of plasmin from plasminogen, tips the balance in favor of extracellular matrix accumulation and promotes fibrosis. Aldosterone receptor antagonism decreases both PAI-1 expression and fibrosis in animal models. These findings have implications for the clinical management of cardiovascular and renal disease.

Aldosterone↗