Altered beta-receptor control of in situ membrane potential in hypertensive rats.

Stekiel, William J.; Contney, Stephen J.; Rusch, Nancy J.

doi:10.1161/01.hyp.21.6.1005

Cited by 36 publications

(34 citation statements)

References 15 publications

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“…The results of the present study are consistent with those of Stekiel and co-workers (33), who demonstrated that in situ arterioles and venules of reduced renal mass hypertensive rats exhibited an impaired hyperpolarization of their VSM cells in response to ␤-adrenergic stimulation with isoproterenol and direct activation of the G s protein with cholera toxin, whereas the electrophysiological response of the vessels to direct activation of adenylyl cyclase with forskolin in that study was unaltered in the hypertensive animals. Subsequent studies (4,14,31) have indicated that impaired coupling between membrane receptors and downstream signal transduction events also occurs in spontaneously hypertensive rats.…”

Section: Effect Of High-salt Diet On Electrical and Mechanical Responsupporting

confidence: 93%

High-salt diet impairs vascular relaxation mechanisms in rat middle cerebral arteries

Lombard

Sylvester

Phillips

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

132

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. High-salt diet impairs vascular relaxation mechanisms in rat middle cerebral arteries. Am J Physiol Heart Circ Physiol 284: H1124-H1133, 2003. First published November 27, 2002 10.1152/ajpheart.00835. 2002-Male Sprague-Dawley rats were maintained on a low-salt (LS) diet (0.4% NaCl) or a high-salt (HS) diet (4% NaCl) for 3 days or 4 wk. PO2 reduction to 40-45 mmHg, the stable prostacyclin analog iloprost (10 pg/ml), and stimulatory G protein activation with cholera toxin (1 ng/ml) caused vascular smooth muscle (VSM) hyperpolarization, increased cAMP production, and dilation in cerebral arteries from rats on a LS diet. Arteries from rats on a HS diet exhibited VSM depolarization and constriction in response to hypoxia and iloprost, failed to dilate or hyperpolarize in response to cholera toxin, and cAMP production did not increase in response to hypoxia, iloprost, or cholera toxin. Low-dose angiotensin II infusion (5 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 iv) restored normal responses to reduced PO2 and iloprost in arteries from animals on a HS diet. These observations suggest that angiotensin II suppression with a HS diet leads to impaired relaxation of cerebral arteries in response to vasodilator stimuli acting at the cell membrane. salt intake; hypertension; angiotensin; hypoxia; vascular smooth muscle; endothelium PREVIOUS STUDIES (8,11,19) have demonstrated that both chronic (4-8 wk) volume expanded hypertension caused by reduced renal mass (RRM) with exposure to a high-salt diet and chronic exposure of normotensive rats to a high-salt diet lead to structural changes in arterioles, reductions in microvessel density, and an impaired relaxation of skeletal muscle resistance vessels in response to a variety of vasodilator stimuli, including reduced PO 2 , the stable prostacyclin analog iloprost, and acetylcholine. Subsequent studies demonstrated that alterations in microvessel structure, density, and reactivity in normotensive animals and RRM hypertensive rats on a high-salt diet develop quite rapidly. For example, Hansen-Smith et al. (15) demonstrated that microvascular rarefaction and profound ultrastructural alterations occur in arterioles of RRM hypertensive rats and normotensive animals after only 3 days on a high-salt diet. Other studies (10)(11)(12)38) have demonstrated that vasodilator responses to reduced PO 2 , acetylcholine, and iloprost are also impaired after short-term exposure to high-salt diet. The microvascular rarefaction and the reduced relaxation of resistance arteries to vasodilator stimuli in animals on a high-salt diet may be related to the angiotensin II (ANG II) suppression that occurs in response to elevated dietary salt intake because both the reduction of cremasteric microvessel density (16) and the impaired dilation of skeletal muscle resistance arteries in response to acetylcholine, iloprost, and reduced PO 2 in animals on a high-salt diet can be prevented by infusion of a low dose of ANG II (37,38).To date, the majority of studies investigating changes in vascular control mechanisms with a highsa...

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Section: Effect Of High-salt Diet On Electrical and Mechanical Responsupporting

confidence: 93%

High-salt diet impairs vascular relaxation mechanisms in rat middle cerebral arteries

Lombard

Sylvester

Phillips

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

132

View full text Add to dashboard Cite

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“…Because stimulation of G,a increases adenylate cyclase activity to mediate /3-adrenergic vasodilation, 1 this downregulation of G,a may help to explain the loss of )S-adrenergic inhibition of arterial tone in RRM rats, which may promote arterial constriction. 19 Furthermore, we have recently noted that pressurization of isolated renal arteries increases inositol trisphosphate levels, a process probably dependent on G q a. The finding in the present study of elevated G q a levels in aortas exposed to high pressure in IR-AC rats raises the possibility that enhanced G q a expression may reflect the increased requirement for this protein for phospholipase C pathway signaling in hypertension.…”

Section: Discussionsupporting

confidence: 51%

Guanine nucleotide-binding proteins in aortic smooth muscle from hypertensive rats.

Zou

Alkayed

et al. 1994

Hypertension

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To explore the hypothesis that altered vascular muscle signal transduction may underlie some of the vascular changes observed in hypertensive models, we measured expression of GTP-binding protein (G protein) o-subunits, G,, G i? and G q , in aortic muscle of reduced renal mass and sham-operated rats and proximal and distal aortic segments from rats with interrenal aortic coarctation (IR-AC). G protein expression was measured by immunoblot analysis. When we probed aortic muscle membrane with G, and G q a-subunit antibodies, we identified 41-and 42-kD immunoreactive proteins, respectively. Three immunoreactive bands specific to G, a-subunit antibody were resolved. Immunoreactive blot densities were compared. In aortic muscle membrane of reduced renal mass rats (blood pressure, 148 ±7 mm Hg), we found significantly reduced G, and G, blot densities compared with sham-operated controls (blood pressure, 99±12 mm Hg). There were no differences in G q blot densities between re-G TP-binding proteins (G proteins) are a family of heterotrimeric proteins composed of a-, /3-, and -y-subunits.1 -2 These regulatory proteins link cell surface receptors to intracellular intermediates and second messengers and thus are vital links and initiators of signal transduction in response to neurotransmitters and endogenous vasoactive agents in vascular smooth muscle. Given the massive literature regarding altered arterial reactivity to a variety of vasoactive substances in animals with experimental hypertension, we conducted the present studies to explore the hypothesis that arterial muscle membranes from rats with surgically induced hypertension show altered G protein expression compared with their normotensive counterparts. Methods Experimental Animal ModelsAdult male Sprague-Dawley rats (weight, 250±8 g; purchased from Sasco) were subjected to 75% reduction in renal mass by a two-stage operation to produce reduced renal mass (RRM) rats.3 -4 Normotensive control rats were subjected to the same surgical procedure except for removal of renal tissue (sham rats). After recovery for 1 week, both RRM and sham rats received a 4% NaCl diet for 2 weeks. Then rats were anesthetized with 40 mg/kg ketamine-HCI (Ketaset, Aveco Co) followed by 20 to 30 mg/kg sodium pentobarbital (Veterinary Labs, Inc). Catheters were placed into the femoral artery duced renal mass and control rats. G, and G, blot densities were significantly lower in IR-AC proximal aortic segments (carotid pressure, 165±5 mm Hg) and distal aortic segments (femoral pressure, 121 ±4 mm Hg) than in aortas of shamoperated controls. In contrast, G q expression was significantly increased in the high-pressure proximal aortic segments compared with low-pressure distal aortic segments from IR-AC rats. Thus, altered G protein expression occurs in aortic muscle from nongenetic rat models of hypertension. Given the differences between reduced renal mass and IR-AC models, it is clear that pressure is not the only variable regulating G protein expression and that hormonal and/or metabol...

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“…1C) was <10 mV more negative than the vascular voltages measured at experimentally advantageous in vivo sites, such as the rat cremaster muscle (−42 mV) and the hamster cheek pouch (−46 mV) (27,28). Thus, a lack of internal pressurization does not account for the suprahyperpolarized membrane potentials of ∼-90 mV that we recorded in arterioles of nonperfused ex vivo <P30 ROP retinas (Fig.…”

Section: Discussionmentioning

confidence: 63%

Bioelectric impact of pathological angiogenesis on vascular function

Puro

Kohmoto

Fujita

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Pathological angiogenesis, as seen in many inflammatory, immune, malignant, and ischemic disorders, remains an immense health burden despite new molecular therapies. It is likely that further therapeutic progress requires a better understanding of neovascular pathophysiology. Surprisingly, even though transmembrane voltage is well known to regulate vascular function, no previous bioelectric analysis of pathological angiogenesis has been reported. Using the perforated-patch technique to measure vascular voltages in human retinal neovascular specimens and rodent models of retinal neovascularization, we discovered that pathological neovessels generate extraordinarily high voltage. Electrophysiological experiments demonstrated that voltage from aberrantly located preretinal neovascular complexes is transmitted into the intraretinal vascular network. With extensive neovascularization, this voltage input is substantial and boosts the membrane potential of intraretinal blood vessels to a suprahyperpolarized level. Coincident with this suprahyperpolarization, the vasomotor response to hypoxia is fundamentally altered. Instead of the compensatory dilation observed in the normal retina, arterioles constrict in response to an oxygen deficiency. This anomalous vasoconstriction, which would potentiate hypoxia, raises the possibility that the bioelectric impact of neovascularization on vascular function is a previously unappreciated pathophysiological mechanism to sustain hypoxia-driven angiogenesis.neovascularization | proliferative retinopathy | retinopathy of prematurity | proliferative diabetic retinopathy | retina T he abnormal growth of blood vessels is a key pathophysiological feature of numerous disorders, including tumorigenesis, arthritis, endometriosis, and retinopathies. Despite substantial progress from studies of patients and animal models, abnormal neovascularization remains a common threat to health and wellbeing. To help address this challenge, we devised a unique experimental approach to better understand neovascular pathophysiology. Because almost nothing is known about the electrogenic profile of neovascular complexes and how these complexes functionally interact with their parent vessels, we focused on the bioelectric features of neovascularization. These gaps in knowledge are surprising, considering that it is well established that the transmembrane voltage of vascular cells (1), as well as electrotonic cell-cell interactions within a vascular network (2-4), play vital roles in regulating blood flow.In this electrophysiological analysis of pathological angiogenesis, we focused on abnormal vasoproliferation in rodent and human retinas. For multiple reasons, the retina is an ideal tissue for this undertaking. First is its clinical importance. Retinal vasoproliferation is the major cause of blindness in prematurely born infants (retinopathy of prematurity) and persons with diabetes (proliferative diabetic retinopathy) and sickle cell disease (sickle cell retinopathy). The hallmark of these disorders is abno...

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Altered beta-receptor control of in situ membrane potential in hypertensive rats.

Cited by 36 publications

References 15 publications

High-salt diet impairs vascular relaxation mechanisms in rat middle cerebral arteries

High-salt diet impairs vascular relaxation mechanisms in rat middle cerebral arteries

Guanine nucleotide-binding proteins in aortic smooth muscle from hypertensive rats.

Bioelectric impact of pathological angiogenesis on vascular function

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