Time Course of Vascular Structural Changes During and After Short-Term Antihypertensive Treatment

Hale, Taben M.; Shoichet, Martin J; Bushfield, Terri L; Adams, Michael

doi:10.1161/01.hyp.0000079309.68998.65

Cited by 23 publications

(36 citation statements)

References 47 publications

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“…Concentrations were determined based on average body weight and water consumption per cage, and adjusted every 5-6 days to account for changes in body weight and daily water consumption, as previously described. 9,10 Rats had ad libitum access to food and water throughout the treatment period. The dose and duration of enalapril treatment was based on previous studies where we demonstrated persistent reductions in blood pressure and LV mass following cessation of treatment 9 and apoptosis-mediated reduction of cardiac fibrobasts in the LV.…”

Section: Animal Proceduresmentioning

confidence: 99%

“…9,10 Rats had ad libitum access to food and water throughout the treatment period. The dose and duration of enalapril treatment was based on previous studies where we demonstrated persistent reductions in blood pressure and LV mass following cessation of treatment 9 and apoptosis-mediated reduction of cardiac fibrobasts in the LV. 5 A 14-day washout period following enalapril treatment based on previous assessments demonstrating that blood pressure stabilizes at a new baseline B7-10 days following cessation of treatment.…”

Section: Animal Proceduresmentioning

confidence: 99%

“…5 Interestingly, this reduction in LV mass as well as arterial pressure have been shown to persist even after treatment cessation. 9 Furthermore, short-term ACE inhibition has also produced kidney-specific changes including reduced renal structurally-based vascular resistance properties that persist long after stopping treatment. 10 In animal models of myocardial infarction, initiating treatment with an ACE inhibitor before and during an ischemic insult results in a reduction in both infarct size and suppression of the inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

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Short-term ACE inhibition confers long-term protection against target organ damage

et al. 2012

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Angiotensin converting enzyme (ACE) inhibitors reduce left ventricular (LV) hypertrophy and cardiovascular-renal fibrosis. Experimentally, changes in the LV and kidney persist even after cessation of treatment. The present study investigates whether brief ACE inhibition in spontaneously hypertensive rats (SHR) provides long-term protection against the LV and kidney damage induced by the nitric oxide synthase inhibitor N-x-nitro-L-arginine-methyl ester (L-NAME). SHR received the ACE inhibitor enalapril (n¼36) or tap water (n¼36). In all, 12 control and treated SHR were sacrificed after 2 weeks and remaining rats were taken off-treatment. After a 2-week washout, 12 controls or previously treated SHR were sacrificed and remaining rats were treated with L-NAME ((control (Con)+L, enalapril (Enal)+L) for 10 days. At sacrifice, blood pressure was recorded via carotid artery cannulation in anesthetized rats, and blood, the kidney and LV were isolated for analysis. LV mass and arterial pressure were significantly reduced by enalapril. LV mass showed a persistent reduction throughout the study. In LV, prior enalapril treatment provided significant (Po0.05) protection against L-NAME-induced increases in proliferating cells (Con+L: 11±10.0 mm 2 vs. Enal+L: 4±4.4 mm 2 ), interstitial fibrosis (Con+L: 3±2.5% vs. Enal+L: 1±1.0%) and tissue macrophages (Con+L: 12±9 mm 2 vs. Enal+L: 5±3.6 mm 2 ). In the kidney, prior enalapril treatment protected against L-NAME-induced interstitial fibrosis and vascular injury. There was no difference in glomerular size or glomerulosclerosis regardless of prior treatment. Plasma creatinine and urea were significantly increased in L-NAME treated rats. This study suggests that brief ACE inhibition confers protection against future heart and kidney injury, even in the absence of continued antihypertensive treatment.

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Section: Animal Proceduresmentioning

confidence: 99%

Section: Animal Proceduresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Short-term ACE inhibition confers long-term protection against target organ damage

et al. 2012

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“…The first is the duration of the cardiovascular effects after treatment withdrawal. Various long-term and also some short-term antihypertensive treatments have been shown to induce persistent changes in blood pressure and cardiovascular structure weeks after treatment removal (38). Therefore, an important question that needs to be addressed is whether the withdrawal of LGF treatment would or not maintain the reduction of blood pressure and the regenerative cardiovascular actions.…”

Section: Limitations Of the Studymentioning

confidence: 99%

Liver growth factor treatment restores cell-extracellular matrix balance in resistance arteries and improves left ventricular hypertrophy in SHR

Conde

González

Quintana‐Villamandos³

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Conde MV, Gonzalez MC, Quintana-Villamandos B, Abderrahim F, Briones AM, Condezo-Hoyos L, Regadera J, Susin C, de Diego JJ, Delgado-Baeza E, Diaz-Gil JJ, Arribas SM. Liver growth factor treatment restores cell-extracellular matrix balance in resistance arteries and improves left ventricular hypertrophy in SHR. Am J Physiol Heart Circ Physiol 301: H1153-H1165, 2011. First published June 3, 2011 doi:10.1152/ajpheart.00886.2010.-Liver growth factor (LGF) is an endogenous albumin-bilirubin complex with antihypertensive effects in spontaneously hypertensive rats (SHR). We assessed the actions of LGF treatment on SHR mesenteric resistance and intramyocardial arteries (MRA and IMA, respectively), heart, and vascular smooth muscle cells (VSMC). SHR and Wistar-Kyoto (WKY) rats treated with vehicle or LGF (4.5 g LGF/rat, 4 ip injections over 12 days) were used. Intra-arterial blood pressure was measured in anesthetized rats. The heart was weighted and paraffinembedded. Proliferation, ploidy, and fibronectin deposition were studied in carotid artery-derived VSMC by immunocytochemistry. In MRA, we assessed: 1) geometry and mechanics by pressure myography; 2) function by wire myography; 3) collagen by sirius red staining and polarized light microscopy, and 4) elastin, cell density, nitric oxide (NO), and superoxide anion by confocal microscopy. Heart sections were used to assess cell density and collagen content in IMA. Left ventricular hypertrophy (LVH) regression was assessed by echocardiography.LGF reduced blood pressure only in SHR. LGF in vitro or as treatment normalized the alterations in proliferation and fibronectin in SHR-derived VSMC with no effect on WKY cells. In MRA, LGF treatment normalized collagen, elastin, and VSMC content and passive mechanical properties. In addition, it improved NO availability through reduction of superoxide anion. In IMA, LGF treatment normalized perivascular collagen and VSMC density, improving the wall-to-lumen ratio. Paired experiments demonstrated a partial regression of SHR LVH by LGF treatment. The effective cardiovascular antifibrotic and regenerative actions of LGF support its potential in the treatment of hypertension and its complications. intramyocardial arteries; mesenteric resistance arteries; nitric oxide; vascular remodeling; left ventricular hypertrophy LIVER GROWTH FACTOR (LGF) was first described as an endogenous factor with mitogenic properties in liver (21).LGF is not detected in physiological conditions, but it increases in plasma in situations of hepato-biliary disorders, both in humans and rats (21,24). The chemical analysis of LGF obtained from human and rat plasma has revealed that it is a covalently bound albumin-bilirubin complex (24,25). The regenerative effects of LGF, initially described in hepato-biliary disorders (22,23,26), have been recently extended to other diseases, such as Parkinson's disease (35, 52), testicular degeneration (51), and pulmonary fibrosis (47).LGF treatment also has cardiovascular effects as previously shown in rodent models of hype...

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“…The concept that long-term antihypertensive therapy with angiotensin-converting enzyme (ACE) inhibitors has been proven to induce both a regression of vascular structure and a reduction in mean arterial pressure, has been recently questioned. 8 Further, the vascular changes that persist off-treatment have been proposed to result from extended inhibition of the trophic actions of angiotensin II, prolonged reduction in mean arterial pressure or from combined effects. Recent evidences suggest that aggressive short-term antihypertensive as well as lipid-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may induce structural remodeling of the penile vasculature.…”

Section: Introductionmentioning

confidence: 99%

Relationship between chronic tadalafil administration and improvement of endothelial function in men with erectile dysfunction: a pilot study

et al. 2006

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Men with erectile dysfunction (ED) frequently have a disproportionate burden of comorbid vascular disorders including atherosclerotic disease. We investigated whether scheduled tadalafil is better than on-demand (OD) in improving endothelium-dependent vasodilatation of cavernous arteries in men with ED and whether this effect is also exerted on markers of endothelial function. We did an open-label, randomized, crossover study including 20 male outclinic patients aged 18 years or older (mean age 54 years) who had at least a 3-month history of ED of any severity or etiology. Tadalafil (20 mg) on alternate days (ADs) or OD was administered for 4 weeks. Primary end points were variations of basal inflow (peak systolic velocity (PSV)) and flow-mediated dilatation (FMD) of cavernous arteries compared with baseline at penile Duplex ultrasound. Secondary end points were variations of Q13-SIEDY scores regarding morning erections and of markers of endothelial function, that is, vascular cell adhesion molecule (VCAM), intercellular cell adhesion molecule, endothelin-1 (ET-1), insulin and C-reactive protein (CRP). PSVs and FMD were higher after AD treatment when compared with OD and baseline, respectively (P ¼ 0.0001), and improvements were maintained from 2 weeks after discontinuation (Po0.005). Patients receiving tadalafil AD experienced a significant improvement of morning erections as compared to AD treatment (Po0.0001); ET1, VCAM and CRP showed a robust decrease after chronic vs OD regimes (Po0.05), with concomitant increase in insulin levels (Po0.05), without any variation in blood pressure and other laboratory parameters. Chronic but not OD tadalafil improves endothelial function with sustained effects from its discontinuation. Chronic treatment also produces a dramatic increase in morning erections, which determines better oxygenation to the penis, thus providing a rationale for vascular rehabilitation.

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Time Course of Vascular Structural Changes During and After Short-Term Antihypertensive Treatment

Cited by 23 publications

References 47 publications

Short-term ACE inhibition confers long-term protection against target organ damage

Short-term ACE inhibition confers long-term protection against target organ damage

Liver growth factor treatment restores cell-extracellular matrix balance in resistance arteries and improves left ventricular hypertrophy in SHR

Relationship between chronic tadalafil administration and improvement of endothelial function in men with erectile dysfunction: a pilot study

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