PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 2060030

Microvascular endothelial-derived autacoids regulate pericyte contractility.

A B Dodge·H B Hechtman·D Shepro
View original source ↗Export metadata ↓

Abstract

A silicone rubber assay is used in conjunction with morphometric measurements to characterize in vitro the contractile properties of retinal pericytes in response to endothelial secreted factors. Factor(s) present in conditioned media derived from pulmonary and retinal microvascular endothelial cells and pulmonary artery endothelial cells promote pericyte contractions. Using a radioimmunoassay significant levels of endothelin immunoreactivity are measured in conditioned media obtained from all three cell lines. Thrombin treatment enhanced endothelin-like secretions by pulmonary microvascular endothelial cells, but significantly reduced levels of endothelin-like immunoreactivity secreted by retinal microvascular endothelial cells. Synthetic endothelin and thromboxane A2 (TxA2) stimulate pericyte contractions, whereas prostaglandin I2 (PGI2) promotes pericyte relaxation. Thrombin and angiotension II (ang II) have no effect on pericyte contractility. However, using cocultures of pericytes and endothelial cells we observe endothelial-dependent pericyte contractions in response to thrombin and ang II. Thrombin and ang II stimulate the release of endothelial-derived contracting factors, with characteristics similar to endothelin. These data suggest microvascular endothelial cell-pericyte interactions may regulate, at least in part, microvessel contractility.

Explore related subjects

Angiotensin IIAnimalsAortaCapillariesCattleCell CommunicationCell MovementCells, CulturedCulture MediaCytoskeletonEndothelinsEndothelium, VascularEpoprostenolLungMicroscopy, Phase-ContrastRadioimmunoassayRetinal VesselsSilicone ElastomersThromboxane A2VenulesJournal ArticleResearch Support, U.S. Gov't, P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

A B Dodge, H B Hechtman, D Shepro. 1991. Microvascular endothelial-derived autacoids regulate pericyte contractility.. https://doi.org/10.1002/cm.970180304

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

p38 mitogen-activated protein kinase inhibition ameliorates angiotensin II-induced target organ damage.

We investigated whether or not p38 mitogen-activated protein kinase inhibition ameliorates angiotensin II-induced target organ damage. We used double transgenic rats harboring both human renin and angiotensinogen genes (dTGRs). dTGR, with or without p38 inhibitor (BIRB796; 30 mg/kg per day in the diet), and nontransgenic Sprague-Dawley rats were studied in 2 protocols. In protocol 1 (week 7), systolic blood pressure of untreated dTGRs was 204+/-4 mm Hg, but partially reduced after BIRB796 treatment (166+/-7 mm Hg), whereas Sprague-Dawley rats were normotensive. The cardiac hypertrophy index was unchanged in untreated and BIRB796-treated dTGRs. The beta-myosin heavy chain expression of BIRB796-treated hearts was significantly lower in BIRB796 compared with dTGRs, indicating a delayed switch to the fetal isoform. BIRB796 treatment significantly reduced cardiac fibrosis, connective tissue growth factor, tumor necrosis factor-alpha, interleukin-6, and macrophage infiltration. Albuminuria was not reduced in BIRB796-treated dTGRs. Tubular and glomerular damage with tumor necrosis factor-alpha expression was unaltered, although serum creatinine and cystatin C were normalized. Renal macrophage infiltration, fibrosis, and vessel damage were reduced. In protocol 2 (week 8), we focused on mortality and arrhythmogenic electrical remodeling. Mortality of untreated dTGRs was 100% but was reduced to 10% in the BIRB796 group. Cardiac magnetic field mapping showed prolongation of depolarization and repolarization in untreated dTGRs compared with Sprague-Dawley rats with a partial reduction by BIRB796. Programmed electrical stimulation elicited ventricular tachycardias in 81% of untreated dTGRs but only in 48% of BIRB796-treated dTGRs. In conclusion, BIRB796 improved survival, target organ damage, and arrhythmogenic potential in angiotensin II-induced target organ damage.

Angiotensin II↗
PubMed2007

Exercise training prevents arterial baroreflex dysfunction in rats treated with central angiotensin II.

Angiotensin II (Ang II)-induced arterial baroreflex dysfunction is associated with superoxide generation in the brain. Exercise training (EX) improves baroreflex function and decreases oxidative stress in cardiovascular diseases linked to elevated central Ang II. The aim of this study was to determine whether previous EX prevents baroreflex impairment caused by central administration of exogenous Ang II via an Ang II-superoxide mechanism. Four groups of rats were used: non-EX artificial cerebrospinal fluid infused, non-EX Ang II infused, EX artificial cerebrospinal fluid infused, and EX Ang II infused. Rats were treadmill trained for 3 to 4 weeks and subjected to intracerebroventricular infusion of Ang II over the last 3 days of EX. Twenty-four hours after the end of EX, the arterial baroreflex was assessed in anesthetized rats. Compared with non-EX artificial cerebrospinal fluid-infused rats, Ang II significantly decreased baroreflex sensitivity (maximum gain: 3.0+/-0.2% of maximum per millimeter of mercury versus 1.6+/-0.1% of maximum per millimeter of mercury; P<0.01), which was abolished by acute intracerebroventricular infusion of the Ang II type 1 receptor antagonist losartan and the reduced nicotinamide-adenine dinucleotide phosphate oxidase inhibitor apocynin. EX prevented the decrease in baroreflex sensitivity and downregulated Ang II type 1 receptor and NADPH oxidase subunit protein expression in the paraventricular nucleus of Ang II-infused rats. Finally, EX decreased superoxide production in the paraventricular nucleus of Ang II-infused rats. These results indicate that EX improves arterial baroreflex function in conditions of high brain Ang II, which is mediated by the central Ang II type 1 receptor and associated with a reduction in central oxidative stress.

Angiotensin II↗
PubMed2007

p22phox in the macula densa regulates single nephron GFR during angiotensin II infusion in rats.

Angiotensin II (ANG II) infusion increases renal superoxide (O(2)(-)) and enhances renal vasoconstriction via macula densa (MD) regulation of tubuloglomerular feedback, but the mechanism is unclear. We targeted the p22(phox) subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) with small-interfering RNA (siRNA) to reduce NADPH oxidase activity and blood pressure response to ANG II in rats. We compared single nephron glomerular filtration rate (SNGFR) in samples collected from the proximal tubule (PT), which interrupts delivery to the MD, and from the distal tubule (DT), which maintains delivery to the MD, to assess MD regulation of GFR. SNGFR was measured in control and ANG II-infused rats (200 ng.kg(-1).min(-1) for 7 days) 2 days after intravenous injection of vehicle or siRNA directed to p22(phox) to test the hypothesis that p22(phox) mediates MD regulation of SNGFR during ANG II. The regulation of SNGFR by MD, determined by PT SNGFR-DT SNGFR, was not altered by siRNA in control rats (control + vehicle, 13 +/- 1, n = 8; control + siRNA, 12 +/- 2 nl/min, n = 8; not significant) but was reduced by siRNA in ANG II-treated rats (ANG II + vehicle, 13 +/- 2, n = 7; ANG II + siRNA, 7 +/- 1 nl/min, n = 8; P < 0.05). We conclude that p22(phox) and NADPH oxidase regulate the SNGFR during ANG II infusion via MD-dependent mechanisms.

Angiotensin II↗