Impaired function of alpha‐2 adrenoceptors in smooth muscle of mesenteric arteries from spontaneously hypertensive rats

Feres, Teresa; Borges, Antônio Carlos Romão; Silva, Eneida de Gusmão; Paiva, Antonio Cechelli de Mattos; Paiva, Therezinha B.

doi:10.1038/sj.bjp.0702177

Cited by 24 publications

(27 citation statements)

References 36 publications

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“…This could be attributed to impaired activity of K ϩ channels, as was observed for the responses to ␣ 2 -adrenergic agonists, 23 rather than to impaired synthesis, release, or diffusion of EDHF.…”

Section: Discussionmentioning

confidence: 99%

“…Since previous studies already reported an interaction between NO and EDHF systems, 23,32 it is likely that the reduced hyperpolarization induced by ACh in untreated SHR mesenteric arteries, due to the impairment of K ϩ channels, may upregulate the production of NO.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously observed that L-NNA (30 mol/L) had no effect on the resting membrane potential of NWR or SHR rings, whereas apamin (100 nmol/L) induced a significant depolarization in rings from NWR but did not affect the resting membrane potential of SHR preparations. 23 …”

Section: Membrane Potentialmentioning

confidence: 99%

“…20 In the case of the rat mesenteric artery, evidence in the literature suggests that apamin-sensitive Ca 2ϩ -dependent K ϩ channels may be the main ion channels mediating the endothelium-dependent hyperpolarizing response to ACh. 21,22 These channels were found to be impaired in mesenteric vessels 23 as well as in other visceral 24 smooth muscles of the SHR. This could be responsible for the reduced endothelium-dependent hyperpolarizing and relaxation responses to ACh in SHR mesenteric arteries, since the role of NO in the response was well preserved, and the participation of prostacyclin in the relaxation appeared to be insignificant.…”

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confidence: 99%

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Effect of Cholecalciferol Treatment on the Relaxant Responses of Spontaneously Hypertensive Rat Arteries to Acetylcholine

et al. 1999

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Abstract-We studied the effect of oral cholecalciferol treatment on the endothelium-dependent vascular relaxation and hyperpolarization induced by acetylcholine (ACh), which is impaired in spontaneously hypertensive rats (SHR). Adult female SHR and normotensive Wistar-Kyoto rat (WKY) controls received 125 g of cholecalciferol per kilogram body weight per day for 6 weeks. The responses to ACh of the isolated mesenteric vascular bed and mesenteric artery rings were measured, as well as the smooth muscle cell membrane potential. After cholecalciferol treatment, the systolic blood pressure and basal perfusion pressure of the mesenteric vascular bed of the SHR fell to control levels. The relaxant and hyperpolarizing effects of ACh, which are reduced in SHR, were also brought to control levels after cholecalciferol treatment. These effects of ACh were inhibited by N -nitro-L-arginine in SHR and by apamin in WKY. After cholecalciferol treatment, SHR hyperpolarizing responses showed the same inhibition pattern as those of WKY. This indicates that, after cholecalciferol treatment, SHR vascular mesenteric preparation responses to ACh are mediated by endothelium-derived hyperpolarizing factor, which induces activation of Ca 2ϩ -dependent K ϩ channels, as in WKY. In untreated SHR, the ACh-mediated response is entirely due to ACh acting via the release of nitric oxide.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Membrane Potentialmentioning

confidence: 99%

mentioning

confidence: 99%

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Effect of Cholecalciferol Treatment on the Relaxant Responses of Spontaneously Hypertensive Rat Arteries to Acetylcholine

et al. 1999

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“…In previous articles, 13,14 we reported that SHR mesenteric artery smooth muscles are less polarized than those of normotensive Wistar rats (NWR). This was attributed to different alterations, such as impairment of the activity of K ϩ channels coupled to ␣ 2 -adrenoceptors or diminished NO production in the SHR.…”

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confidence: 99%

Role of Membrane Potential and Expression of Endothelial Factors in Restenosis After Angioplasty in SHR

et al. 2004

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Abstract-We examined the roles played by impaired K ϩ channels, diminished nitric oxide (NO) production, endothelin release, and smooth muscle membrane potential in the increased restenosis observed in spontaneously hypertensive rat (SHR) carotid arteries after angioplasty. The SHR carotid was found to be less polarized than that of normotensive Wistar rats (NWR), and it was further depolarized by the ␣ 2 agonist UK 14,304. This response was blocked by iberiotoxin, indicating that calcium-dependent K ϩ channels operate normally in the SHR carotid. Acetylcholine caused a hyperpolarization that was significantly smaller in SHR than in NWR carotids, indicating a deficient release of NO in the SHR. After angioplasty, SHR and NWR vessels were depolarized, returning to baseline after 10 days. In the SHR but not in the NWR the contralateral carotid was also depolarized, and this was prevented by the endothelin A/B receptor antagonist bosentan. After angioplasty, endothelin-1 plasma levels increased in both SHR and NWR, but the increase was significantly more prolonged in SHR. We found that the more pronounced restenosis observed in the SHR carotid after angioplasty is not due to impairment of calcium-dependent K ϩ channels but is related to the relatively depolarized vascular smooth muscles, involving endothelin release caused by reduced NO levels in that strain. Key Words: rats, spontaneously hypertensive Ⅲ angioplasty Ⅲ carotid arteries Ⅲ muscle smooth, vascular Ⅲ membranes Ⅲ endothelin T he vascular endothelium plays a role in blood flow control through the release of relaxant and contractile factors. Thus, to prevent overactivation of contractile responses, it releases relaxant factors such as endotheliumderived hyperpolarizing factor, prostanoids, and nitric oxide (NO). The endothelium also prevents the development of vascular lesions by inhibiting platelet aggregation, leukocyte adhesion, and proliferation of vascular smooth muscle cells. 1 This protective role is altered in pathological conditions such as arterial hypertension, which is characterized by cell permeability changes, leukocyte adhesion, and smooth muscle cell proliferation. Also, the repair mechanism designed to restore the vessel wall after damage from different causes frequently escapes self-limiting control, resulting in lumen narrowing caused by smooth muscle cell proliferation. These processes are the precursors of atherosclerotic plaque formation, which leads to increased vascular resistance and to restenosis. 2 Procedures such as atherectomy performed by balloon injury (angioplasty) widen the lumen but cause extensive endothelium destruction, leaving the vascular wall without protection. This injury stimulates medial smooth muscle cell proliferation and migration to the deendothelized surface to form a neointima. Neointima proliferation and subsequent vascular restenosis are believed to be the main events in the initiation of the atherosclerosis that limits the long-term efficacy of percutaneous transluminal coronary angioplasty. 3 It is well...

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Vitamin D deficiency and essential hypertension

Chen

Sun

Agrawal

2015

Journal of the American Society of Hypertension

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Essential hypertension (EH) results when the balance between vasoconstriction and vasodilation is shifted in favor of vasoconstriction. This balance is controlled by the interaction of genetic and epigenetic factors. When there is an unstable balance, vitamin D deficiency as an epigenetic factor triggers a shift to the side of vasoconstriction. In this article, we critically analyze clinical findings on the effect of vitamin D on blood pressure, combined with progress in molecular mechanisms. We find that vitamin D repletion exerts a clinically significant antihypertensive effect in vitamin D-deficient EH patients. Of note, a few trials reported no antihypertensive effect from vitamin D due to suboptimal study design. Short-term vitamin D supplementation has no effect on blood pressure in normotensive subjects. This could explain the mixed results and may provide a theoretical basis for future trials to identify beneficial effects of vitamin D in intervention for EH. KeywordsEssential Hypertension; Vitamin D; Clinical Trial; Molecular Mechanism Essential Hypertension (EH)One billion people worldwide suffer from hypertension (HTN) [1]. Of these patients, 95% have hypertension of unknown etiology, called essential hypertension (EH), and cannot maintain normal blood pressure (BP) without daily treatment [2]. Many signaling pathways are involved in BP regulation in EH. These include the angiotensin II (Ang II)-sympathetic nerve-CD4 + T cell system [3], a pathway consisting of a series of genes participating in the control of renal salt handling [4], and pathways mediating constriction and dilation of vascular smooth muscle (VSM) cells [5,6]. Dysfunction of any one of these pathways leads to increased VSM tone and remodeling in resistance arteries, resulting in high BP. However, Address correspondence to: Songcang Chen MD, Assistant Professor, Center for Clinical & Translational Science, 2500 California Plaza, Omaha, NE USA 68178, Ph: (402) 280-3488, SongcangChen@creighton.edu. Potential conflicts of interest/financial disclosure: None All authors have read the journal's authorship agreement and publication policy and declare no conflict of interest.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript the exact etiology and pathogenesis of EH is poorly understood, leading to nonspecific and less-effective treatment. In America, 50% of hypertensive patients (∼68 million) do not have their BP well-controlled and about 5 million patients are resistant to antihypertensive treatment with a c...

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Impaired function of alpha‐2 adrenoceptors in smooth muscle of mesenteric arteries from spontaneously hypertensive rats

Cited by 24 publications

References 36 publications

Effect of Cholecalciferol Treatment on the Relaxant Responses of Spontaneously Hypertensive Rat Arteries to Acetylcholine

Effect of Cholecalciferol Treatment on the Relaxant Responses of Spontaneously Hypertensive Rat Arteries to Acetylcholine

Role of Membrane Potential and Expression of Endothelial Factors in Restenosis After Angioplasty in SHR

Vitamin D deficiency and essential hypertension

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