Effect of different drug classes on reverse remodeling of intramural coronary arterioles in the spontaneously hypertensive rat

Mancini, Massimiliano; Scavone, Angela; Sartório, Carmem Luíza; Baccaro, Rocco; Kleinert, Christina; Pernazza, Angelina; Buia, Veronica; Leopizzi, Martina; d’Amati, Giulia; Camici, Paolo G.

doi:10.1111/micc.12298

Cited by 9 publications

(4 citation statements)

References 57 publications

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“…It is also conceivable that amlodipine and candesartan may genuinely lack substantial microvascular effects as other studies have shown that treatment with amlodipine did not improve coronary flow reserve in hypertensive patients [33,34]. Similarly in the spontaneously hypertensive rat amlodipine and candesartan did not show any significant reverse arteriolar remodeling compared to placebo [35].…”

Section: Discussionmentioning

confidence: 95%

Effects of Candesartan versus Amlodipine on Capillary Rarefaction, Pulse Wave Velocity and Central Blood Pressure in Patients with Essential Hypertension

Raghuraman¹,

Carney²,

Mullahy³

et al. 2017

NIVI

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Background: A reduction in the density of capillaries (rarefaction) is known to occur in many tissues in patients with essential hypertension and play a role in increasing Blood Pressure (BP). The aim of this trial was to assess in a randomized, double blind, design the effects of treatment of hypertension with candesartan versus amlodipine on microvascular rarefaction and other indices of vascular function. Methods: We recruited twenty-two individuals with mild-to-moderate hypertension. After a 2-week placebo run-in period, patients who remained hypertensive (≥140/90 mmHg) were randomized to 8-weeks treatment with Candesartan tablets 8mg daily (with forced titration to 16mg) or Amlodipine tablets 5mg daily (with forced titration to 10mg). The capillary microcirculation was studied using Cap-iScope system CAM1. Pulse wave velocity, central BP and aortic Augmentation Index were also measured. Results: We observed significant reductions in brachial BP, and central BP after 4 and 8 weeks treatment with either candesartan or amlodipine but there was no significant effect on basal (functional) or maximal (structural) capillary densities, or pulse wave velocity. Conclusion: Eight weeks treatment of hypertension with either amlodipine or candesartan significantly reduced brachial and central BP but was not sufficient to induce a regression in functional or structural microvascular abnormalities.

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Section: Discussionmentioning

confidence: 95%

Effects of Candesartan versus Amlodipine on Capillary Rarefaction, Pulse Wave Velocity and Central Blood Pressure in Patients with Essential Hypertension

Raghuraman¹,

Carney²,

Mullahy³

et al. 2017

NIVI

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“…According to the JNC8 guidelines, ACE inhibitors and ARBs are considered first‐line antihypertensive pharmacotherapies . Antihypertensive drugs targeting the RAS may have beneficial peripheral vascular effects . RAS‐specific pharmacotherapy increases eNOS expression in rodent models and improves endothelial function in humans .…”

Section: Introductionmentioning

confidence: 99%

“…27 Antihypertensive drugs targeting the RAS may have beneficial peripheral vascular effects. [28][29][30][31] RAS-specific pharmacotherapy increases eNOS expression in rodent models 32,33 and improves endothelial function in humans. 34,35 RAS-targeted treatment also improves indices of microvessel structure, including reversing rarefaction.…”

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confidence: 99%

Blood pressure normalization via pharmacotherapy improves cutaneous microvascular function through NO‐dependent and NO‐independent mechanisms

2017

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Hypertension is associated with endothelial dysfunction and vascular remodeling. Objective To assess effects of antihypertensive pharmacotherapy on eNOS and iNOS-dependent mechanisms and maximal vasodilator capacity in the cutaneous microvasculature. Methods Intradermal microdialysis fibers were placed in 15 normotensive (SBP 111±2 mmHg), 12 unmedicated hypertensive (SBP 142±2 mmHg), and 12 medicated hypertensive (SBP 120±2 mmHg) subjects. Treatments were control, iNOS-inhibited (1400w), and NOS-inhibited (L-NAME). Red cell flux, measured during local heating (42°C) and acetylcholine (ACh) dose-response protocols, was normalized to cutaneous vascular conductance (CVC=flux•MAP−1) and a percentage of maximal vasodilation (%CVCmax). Results Compared to normotensives, ACh-mediated vasodilation was attenuated in the hypertensive (p<0.001), but not medicated subjects (p=0.83). NOS inhibition attenuated ACh-mediated vasodilation in normotensives compared to hypertensive (p<0.001) and medicated (p<0.001) subjects. With iNOS inhibition there was no difference in ACh-mediated vasodilation between groups. Compared to the normotensives, local heat-induced vasodilation was attenuated in the hypertensives (p<0.001), but iNOS inhibition augmented vasodilation in the hypertensives so this attenuation was abolished (p=0.31). Compared to normotensives, maximal vasodilator capacity was reduced in the hypertensive (p=0.014) and medicated subjects (p=0.004). Conclusion In the cutaneous microvasculature, antihypertensive pharmacotherapy improved endothelial function through NO-dependent and independent mechanisms, but did not improve maximal vasodilator capacity.

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“…In his primary research article, Paolo Camici and colleagues investigate the effect of eight different antihypertensive drugs on the coronary microcirculation in spontaneous hypertensive rats. They found that antihypertensive treatment on CMD is not only dependent on blood pressure reduction, but that compounds with comparable antihypertensive efficacy may exert different effects on hyperemic coronary blood flow and induce different degrees of reverse arteriolar remodeling.…”

mentioning

confidence: 99%

Microvessels of the heart: Formation, regeneration, and dysfunction

Spyridopoulos

Arthur

2017

Microcirculation

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This issue of microcirculation focusses on the special topic of "microvessels of the heart" and contains five state-of-the-art reviews and one expert article that reflect current efforts to address the major gaps in our understanding of these key microvessels. In the adult heart, most attention until recently (especially among the clinical cardiology community) has been given to the main coronary arteries, which are the culprit vessels in patients with coronary artery disease, including its most serious manifestation, acute MI. However, due to major advances in efficiently reopening the acutely blocked coronary arteries, MI is no longer the killer disease it once was. In contrast, there are few treatment options for patients who develop microvascular obstruction during acute MI. Indeed, we have a very poor understanding of this disease, or even how heart vessels are initially formed in development. This is surprising in light of the essential nature of the cardiac microvessels for efficient cardiac function throughout life. The articles in this issue are from six keynote speakers at the 66th annual meeting of the BMS at Newcastle University and review our understanding of these key vessels from initial development to their role in adult heart disease.

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Effect of different drug classes on reverse remodeling of intramural coronary arterioles in the spontaneously hypertensive rat

Abstract: The effect of antihypertensive treatment on CMD is not exclusively dependent on BP reduction. Compounds with comparable antihypertensive efficacy may exert different effects on CF and induce different degrees of reverse arteriolar remodeling.

Cited by 9 publications

References 57 publications

Effects of Candesartan versus Amlodipine on Capillary Rarefaction, Pulse Wave Velocity and Central Blood Pressure in Patients with Essential Hypertension

Effects of Candesartan versus Amlodipine on Capillary Rarefaction, Pulse Wave Velocity and Central Blood Pressure in Patients with Essential Hypertension

Blood pressure normalization via pharmacotherapy improves cutaneous microvascular function through NO‐dependent and NO‐independent mechanisms

Microvessels of the heart: Formation, regeneration, and dysfunction

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