Vascular structural and functional changes: their association with causality in hypertension: models, remodeling and relevance.

Essential hypertension is a complex multifactorial disease process that involves the interaction of multiple genes at various loci throughout the genome, and the influence of environmental factors such as diet and lifestyle, to ultimately determine long-term arterial pressure. These factors converge with physiological signaling pathways to regulate the set-point of long-term blood pressure. In hypertension, structural changes in arteries occur and show differences within and between vascular beds, between species, models and sexes.

Mas receptors in modulating relaxation induced by perivascular adipose tissue.

Aims: Perivascular adipose tissue (PVAT) is known to secrete vascular relaxation factors, and angiotensin 1-7 [Ang-(1-7)] acting on the endothelium is one of the endothelium-dependent relaxation factors. Mas protein is the receptor for Ang-(1-7). Using aorta from Mas-knockout (K/O) and wild type (FVB) mice, we wished to establish the essential role of Mas receptors in mediating the endothelium-dependent relaxation response induced by relaxation factors from PVAT.

The mechanisms of propofol-induced vascular relaxation and modulation by perivascular adipose tissue and endothelium.

Background: Propofol causes hypotension due to relaxation of vascular smooth muscle cells through its direct or indirect vasodilator effects. Perivascular adipose tissue (PVAT) and endothelium attenuate vascular contraction, and the function of PVAT is altered in hypertension and diabetes. Whether PVAT affects the action of anesthetics on vascular function is unknown.

Alterations in perivascular adipose tissue structure and function in hypertension.

We studied the structural and the functional alterations of perivascular adipose tissue (PVAT) in hypertension with spontaneously hypertensive rats (SHR). Measured with dual energy X-ray absorptiometry, a smaller body fat mass and a greater lean mass were found in SHR than in Wistar-Kyoto (WKY) rats, while body weight was comparable between them. In the thoracic PVAT, the density and the total number of brown adipocytes were greater in SHR than in WKY rats, while the cross section area of PVAT was similar between them.

Modulation of vein function by perivascular adipose tissue.

Although a number of studies have shown that perivascular adipose tissue (PVAT) attenuates arterial contraction through the release of perivascular-derived relaxation factors (PVRF), the role of PVAT in modulating venous function and its mechanism(s) remained unknown. Here we examined the role of PVAT in the modulation of vascular function in the inferior vena cava. Venous rings from male Wistar rats were prepared with both endothelium and PVAT intact, with either PVAT or endothelium removed, or with both endothelium and PVAT removed for functional studies.

Mechanisms for perivascular adipose tissue-mediated potentiation of vascular contraction to perivascular neuronal stimulation: the role of adipocyte-derived angiotensin II.

In rat mesenteric arteries we have recently found that perivascular adipose tissue (PVAT) promoted vasoconstriction to perivascular neuronal activation (by electrical field stimulation, EFS) through generation of superoxide. In this study, we examined the role of adipocyte-generated angiotensin II in PVAT-mediated potentiation of contraction to nerve stimulation. In rat mesenteric PVAT, the presence of angiotesinogen and angiotensin I-converting enzyme (ACE) mRNA was confirmed by RT-PCR.

Alteration of perivascular adipose tissue function in angiotensin II-induced hypertension.

We studied the role of perivascular adipose tissue (PVAT) in the control of vascular function in an in vivo experimental model of hypertension produced by angiotensin II infusion by osmotic minipump in adult male Wistar rats. Two weeks after infusion with angiotensin II, blood pressure in treated rats was significantly elevated but heart rate was reduced compared with control rats infused with physiological saline. Contraction of aorta from the 2 groups of rats in response to phenylephrine or serotonin was significantly attenuated by the presence of PVAT in both the presence and absence of endothelium.

Endothelium-dependent relaxation factor released by perivascular adipose tissue.

Objective: Recent studies have demonstrated that perivascular adipose tissue (PVAT) releases vascular relaxation factor(s), but the identity of this relaxation factor remains unknown. Here, we examined if angiotensin 1-7 [Ang-(1-7)] is one of the relaxation factors released by PVAT.

Method: Morphological and functional methods were used to study aorta from adult Wistar rats.

Arterial internal elastic lamina holes: relationship to function?

Internal elastic lamina (IEL) hole (fenestration) characteristics and myoendothelial gap junction (MEGJ) density were examined in selected resistance and conduit arteries of normal and diseased rat and mouse models, using conventional, ultrastructural and confocal microscopy methods. Selected vessels were those commonly used in functional studies: thoracic aorta, proximal and distal mesenteric, caudal, saphenous, middle-cerebral and caudal cerebellar artery. Rat and mouse strains and treatment groups examined were Dahl, Sprague Dawley, Wistar Kyoto, Wistar, spontaneously hypertensive (SHR), deoxycorticosterone (DOC) treated rat; and apolipoprotein E knockout, C57/BL6 and BALB/c mice.

Effects of hyperglycemia on the modulation of vascular function by perivascular adipose tissue.

Objective: To study the acute and chronic effect of hyperglycemia on perivascular adipose tissue (PVAT) function in rat aorta.

Method: Alterations in PVAT function in rat aorta incubated with 22 mmol/l D-glucose for 30 min and in aorta from streptozotocin (STZ)-induced diabetic rats were studied.

Results: Incubation with D-glucose caused an attenuation of contraction in response to phenylephrine, both in the presence and absence of endothelium, whereas removal of PVAT eliminated this attenuation effect.

Flow-induced vascular remodeling in the mesenteric artery of spontaneously hypertensive rats.

The effect of an increased blood flow on vascular remodeling was studied in the mesenteric arteries of 11-12-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY). Increased blood flow was induced by selective ligation of mesenteric arteries. Nearby arteries with normal blood flow were used as controls.

Effects of fetal and neonatal exposure to nicotine on blood pressure and perivascular adipose tissue function in adult life.

In Wistar rats, maternal exposure to nicotine was shown to impair the inhibitory function of perivascular adipose tissue on vascular contractility in the aorta of the offspring. It is not known whether an impairment of perivascular adipose tissue function occurs in smaller arteries, and whether the control of blood pressure is affected. Here we studied the blood pressure effects and the alteration of perivascular adipose tissue function in mesenteric arteries of the offspring born to Wistar-Kyoto rat (WKY) dams exposed to nicotine.

Superoxide anion mediates angiotensin II-induced potentiation of contractile response to sympathetic stimulation.

Angiotensin II is known to potentiate vasoconstriction induced by electrical field stimulation (EFS), but the underlying mechanisms for this potentiation are not fully understood. This study was designed to investigate the role of superoxide anion in the potentiation effects of angiotensin II. Contraction of rat mesenteric arterial segments was induced by perivascular nerve stimulation with EFS, and superoxide production was measured with lucigenin-enhanced chemiluminescence.

Elevated blood pressure in transgenic lipoatrophic mice and altered vascular function.

The role of perivascular fat in the control of vascular function was studied using lipoatrophic A-ZIP/F1 transgenic mice. Only a small amount of brown fat was found around the aorta but not around mesenteric arteries. Blood pressure of A-ZIP/F1 mice became higher than wild-type (WT) mice from 10 weeks of age.

Perivascular adipose tissue promotes vasoconstriction: the role of superoxide anion.

Objectives: Recent studies have demonstrated that perivascular adipose tissue (PVAT) releases vascular relaxation factor(s). In this study, we examined if PVAT releases other vasoactive factors in response to perivascular nerve activation by electrical field stimulation (EFS).

Methods And Results: In Wistar-Kyoto rats, rings of superior mesenteric artery (MA) with intact PVAT (PVAT (+)) showed a greater contractile response to EFS than rings with PVAT removed (PVAT (-)).

Alterations in hypertensive arteries.

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Hydrogen peroxide is an endothelium-dependent contracting factor in rat renal artery.

In addition to endothelium-derived relaxing factor and hyperpolarizing factor, vascular endothelium also modulates smooth muscle tone by releasing endothelium-derived contracting factor(s) (EDCF), but the identity of EDCF remains obscure. We studied here the involvement of hydrogen peroxide (H2O2) in endothelium-dependent contraction (EDC) of rat renal artery to acetylcholine (ACh). ACh (10(-6), 10(-5), and 10(-4) M) induced a transient contraction of rat renal artery with intact endothelium in a concentration-related manner, but not in the artery with endothelium removed.

Perivascular adipose tissue modulates vascular function in the human internal thoracic artery.

Objective: Recent studies have shown that perivascular adipose tissue from the rat aorta secretes a substance that can dilate the aorta. The purpose of the present study was to examine whether this vasodilator is also present in human internal thoracic arteries.

Methods: Vascular function of human internal thoracic arteries with and without perivascular adipose tissue was assessed with wire myography, and morphology was examined with light microscopy.

The effects of quinapril and atorvastatin on artery structure and function in adult spontaneously hypertensive rats.

We studied the combined treatment effects of quinapril and atorvastatin on blood pressure and structure and function of resistance arteries from adult spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY rats). Apoptotic cells were identified by in situ end labeling using the terminal deoxynucleotide transferase-mediated dUTP nick end labeling method. Vascular structure was measured using a morphometric protocol and confocal microscopy and a pressurized artery system was used to study vascular functions.

Alteration of arterial smooth muscle potassium channel composition and BKCa current modulation in hypertension.

We investigated K+ currents and their regulation by the sarcoplasmic reticulum in mesenteric arterial smooth muscle cells of the spontaneously hypertensive rat (SHR). Using perforated patch-clamp technique, we found the overall K+ current density was significantly lower in adult SHR compared to adult Wistar-Kyoto rats (WKY). The K+ currents were almost exclusively of large-conductance Ca2+-dependent (BK(Ca)) variety in SHR, but largely of voltage-gated (Kv) variety in WKY.

Prenatal exposure to nicotine causes postnatal obesity and altered perivascular adipose tissue function.

Objective: Recent epidemiological studies have shown that there is an increased risk of obesity and hypertension in children born to women who smoked during pregnancy. The aim of this study was to examine the effect of fetal and neonatal exposure to nicotine, the major addictive component of cigarette smoke, on postnatal adiposity and blood vessel function.

Research Methods And Procedures: Female Wistar rats were given nicotine or saline (vehicle) during pregnancy and lactation.

Quinapril effects on resistance artery structure and function in hypertension.

The effects of chronic treatment with quinapril on blood pressure, vascular reactivity and structure of resistance arteries were examined in adult, male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. SHR and WKY at 15 weeks of age were treated with quinapril (10 mg/kg per day) for 10 weeks. Structural changes in the mesenteric arteries were measured by optical sectioning with confocal microscopy and in renal arteries by light microscopic measurements.

Control of vascular changes by renin-angiotensin-aldosterone system in salt-sensitive hypertension.

The purpose of this study was to investigate the role of the renin-angiotensin-aldosterone system in hypertension development and cardiovascular structural changes in a salt-sensitive hypertensive model induced by capsaicin (CAP). Newborn male Wistar rats were injected with either capsaicin or vehicle. After weaning at 3 weeks, these rats were divided into the following six treatment groups: capsaicin plus high-salt diet (CAP+HS), control plus high-salt diet (CON+HS), control plus normal salt diet (CON+NS), capsaicin plus high-salt diet and telmisartan (CAP+HS+T, 10 mg/kg/day), capsaicin plus high-salt diet and perindopril (CAP+HS+P, 2 mg/kg/day), and capsaicin plus high-salt diet and spironolactone (CAP+HS+S, 80 mg/kg/day).