Regression of Small Resistance Artery Structural Alterations in Hypertension by Appropriate Antihypertensive Treatment

Agabiti‐Rosei, Enrico; Rizzoni, Damiano

doi:10.1007/s11906-010-0093-7

Cited by 20 publications

(8 citation statements)

References 29 publications

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“…38 SAE can increase as a result of functional vasodilation, such as nitric oxide enhancement or norepinephrine or angiotensin inhibition, or by reversal of structural remodeling. 39 As vasodilation should occur early in pharmacologic studies, and structural changes should be delayed, the 3 and 9 month study time points were designed to separate functional from possible structural effects of the drug administration. In DETECT there was no evidence to support an additional structural vascular effect in addition to the early functional effect.…”

Section: Discussionmentioning

confidence: 99%

Effect of carvedilol, lisinopril and their combination on vascular and cardiac health in patients with borderline blood pressure: the DETECT Study

et al. 2012

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Antihypertensive therapy is aimed at improving vascular and cardiac health, as well as lowering blood pressure (BP). The benefit of such drugs in untreated patients with borderline BP has not been demonstrated. Subjects with BPs ≥130 mm Hg systolic or ≥85 mm Hg diastolic and at least one additional risk factor were randomly assigned to treatment with carvedilol, lisinopril, their combination or placebo. Cardiovascular health was assessed by a disease score (DS), which combines the following tests of cardiovascular function and structure: resting BP, large- and small-artery elasticity (SAE), BP response to exercise, retinal vasculature analysis, electrocardiogram, carotid intima-medial thickness, left ventricular mass, microalbuminuria and N-terminal pro B-type natriuretic peptide. DS was assessed at baseline, after 3 and 9 months of therapy and 1 month after discontinuation of therapy. All active treatment groups displayed a sustained reduction in BP during 9 months of treatment, with the greatest reduction in the cardvedilol+lisinopril group. DS and SAE improved in all the treatment groups but the changes were of borderline significance and exhibited no evidence for progressive improvement from 3 months (functional) to 9 months (structural). All changes were reversed within 1 month after discontinuation of therapy. We conclude that 9 months of treatment with carvedilol, lisinopril or their combination produce a sustained and well-tolerated functional improvement but not a structural improvement, perhaps because of a lack of the nitric oxide-enhancing effects of other agents that inhibit structural changes in the vasculature.

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Section: Discussionmentioning

confidence: 99%

Effect of carvedilol, lisinopril and their combination on vascular and cardiac health in patients with borderline blood pressure: the DETECT Study

et al. 2012

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“…Regression of these changes is a goal of antihypertensive therapy [2] and is associated with reduced incidence of cardiovascular events [3, 4]. Chronic treatment with antihypertensive agents (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium antagonists, β -blockers, and diuretics) has led to regression of vascular remodeling both in humans and in animal models of hypertension [2, 5, 6]. However, early regression of coronary artery remodeling after short-term therapy with these agents has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Short-Term Esmolol Improves Coronary Artery Remodeling in Spontaneously Hypertensive Rats through Increased Nitric Oxide Bioavailability and Superoxide Dismutase Activity

Arnalich-Montiel

González

Delgado-Baeza

et al. 2014

BioMed Research International

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The aim of this study was to assess the effects of short-term esmolol therapy on coronary artery structure and function and plasma oxidative stress in spontaneously hypertensive rats (SHR). For this purpose, 14-month-old male SHR were treated for 48 hours with esmolol (SHR-E, 300 μg/kg/min). Age-matched untreated male SHR and Wistar Kyoto rats (WKY) were used as hypertensive and normotensive controls, respectively. At the end of intervention we performed a histological study to analyze coronary artery wall width (WW), wall-to-lumen ratio (W/L), and media cross-sectional area (MCSA). Dose-response curves for acetylcholine (ACh) and sodium nitroprusside were constructed. We also assessed several plasma oxidative stress biomarkers, namely, superoxide scavenging activity (SOSA), nitrites, and total antioxidant capacity (TAC). We observed a significant reduction in WW (P < 0.001), W/L (P < 0.05), and MCSA (P < 0.01) and improved endothelium-dependent relaxation (AUCSHR-E = 201.2 ± 33 versus AUCSHR = 97.5 ± 21, P < 0.05) in SHR-E compared with untreated SHR; no differences were observed for WW, MCSA, and endothelium-dependent relaxation by ACh at higher concentrations (10−6 to 10−4 mol/l) for SHR-E with respect to WKY. SOSA (P < 0.001) and nitrite (P < 0.01) values were significantly higher in SHR-E than in untreated SHR; however, TAC did not increase after treatment with esmolol. Esmolol improves early coronary artery remodeling in SHR.

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“…Such effects can exacerbate vasoconstriction and elevate vascular resistance and BP; hence, treatment strategies to reduce high BP have long involved the use of Ltype VGCC inhibitors (Sonkusare et al, 2006). Further, Ca 2+ channel blockers which dilate resistance arteries have been shown to reverse eutrophic remodelling (Schiffrin, 2004;Agabiti-Rosei & Rizzoni, 2010). Taken together this suggests that therapies which target intracellular calcium homeostasis are worthy of exploration.…”

Section: Mechanisms Controlling Arterial Contractility; Role Of Intramentioning

confidence: 99%

“…The resistance vasculature is an important target for anti-hypertensive therapies and indeed elevated cardiovascular risk remains despite a reduction of BP if inward remodelling of the microcirculation is not reversed (Buus et al, 2013). Calcium channel blockers, and indeed other anti-hypertensive therapies (ACE inhibitors, angiotensin II receptor blockers) have beneficial effects on both BP and small artery structure, others, including diuretics, have little effect on arterial structure (Schiffrin, 2004;Agabiti-Rosei & Rizzoni, 2010). Given the relation to cardiovascular risk, regression of small artery remodelling is an important goal for the development of new anti-hypertensive therapies alongside BP reduction.…”

Section: Treatment Strategies and Future Directionsmentioning

confidence: 99%

Plasma membrane calcium ATPases (PMCAs) as potential targets for the treatment of essential hypertension

Little

Cartwright

Neyses

et al. 2016

Pharmacology & Therapeutics

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The incidence of hypertension, the major modifiable risk factor for cardiovascular disease, is increasing. Thus, there is a pressing need for the development of new and more effective strategies to prevent and treat hypertension. Development of these relies on a continued evolution of our understanding of the mechanisms which control blood pressure (BP). Resistance arteries are important in the regulation of total peripheral resistance and BP; changes in their structure and function are strongly associated with hypertension. Anti-hypertensives which both reduce BP and reverse changes in resistance arterial structure reduce cardiovascular risk more than therapies which reduce BP alone. Hence, identification of novel potential vascular targets which modify BP is important. Hypertension is a multifactorial disorder which may include a genetic component. Genome wide association studies have identified ATP2B1, encoding the calcium pump plasma membrane calcium ATPase 1 (PMCA1), as having a strong association with BP and hypertension. Knockdown or reduced PMCA1 expression in mice has confirmed a physiological role for PMCA1 in BP and resistance arterial regulation. Altered expression or inhibition of PMCA4 has also been shown to modulate these parameters. The mechanisms whereby PMCA1 and 4 can modulate vascular function remain to be fully elucidated but may involve regulation of intracellular calcium homeostasis and/or comprise a structural role. However, clear physiological links between PMCA and BP, coupled with experimental studies directly linking PMCA1 and 4 to changes in BP and arterial function, suggest that they may be important targets for the development of new pharmacological modulators of BP.

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Regression of Small Resistance Artery Structural Alterations in Hypertension by Appropriate Antihypertensive Treatment

Cited by 20 publications

References 29 publications

Effect of carvedilol, lisinopril and their combination on vascular and cardiac health in patients with borderline blood pressure: the DETECT Study

Effect of carvedilol, lisinopril and their combination on vascular and cardiac health in patients with borderline blood pressure: the DETECT Study

Short-Term Esmolol Improves Coronary Artery Remodeling in Spontaneously Hypertensive Rats through Increased Nitric Oxide Bioavailability and Superoxide Dismutase Activity

Plasma membrane calcium ATPases (PMCAs) as potential targets for the treatment of essential hypertension

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