Functional alterations in cerebrovascular K+ and Ca2+ channels are comparable between simulated microgravity rat and SHR

2005 ◽  
Vol 289 (3) ◽  
pp. H1265-H1276 ◽  
Author(s):  
Man-Jiang Xie ◽  
Li-Fan Zhang ◽  
Jin Ma ◽  
Hong-Wei Cheng
Keyword(s):  
Current Density ◽  
Cell Voltage ◽  
Sprague Dawley ◽  
Experimental Conditions ◽  
Cardiovascular Research ◽  
Spontaneously Hypertensive ◽  
Voltage Dependent ◽  
Current Densities ◽  
Wistar Kyoto ◽  
And Control

Exposure to microgravity leads to a sustained elevation in transmural pressure across the cerebral vasculature due to removal of hydrostatic pressure gradients. We hypothesized that ion channel remodeling in cerebral vascular smooth muscle cells (VSMCs) similar to that associated with hypertension may occur and play a role in upward autoregulation of cerebral vessels during microgravity. Sprague-Dawley rats were subjected to 4-wk tail suspension (Sus) to simulate the cardiovascular effect of microgravity. Large-conductance Ca2+-activated K+ (BKCa), voltage-gated K+ (KV), and L-type voltage-dependent Ca2+ (CaL) currents of Sus and control (Con) rat cerebral VSMCs were investigated with a whole cell voltage-clamp technique. Under the same experimental conditions, KV, BKCa, and CaL currents of cerebral VSMCs from adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were also investigated. KV current density decreased in Sus rats vs. Con rats [1.07 ± 0.14 ( n = 22) vs. 1.31 ± 0.28 ( n = 16) pA/pF at +20 mV ( P < 0.05)] and BKCa and CaL current densities increased [BKCa: 1.70 ± 0.37 ( n = 23) vs. 0.88 ± 0.22 ( n = 19) pA/pF at +20 mV ( P < 0.05); CaL: −2.17 ± 0.21 ( n = 35) vs. −1.31 ± 0.10 ( n = 26) pA/pF at +10 mV ( P < 0.05)]. Similar changes were also observed in SHR vs. WKY cerebral VSMCs: KV current density decreased [1.03 ± 0.33 ( n = 9) vs. 1.62 ± 0.64 ( n = 9) pA/pF at +20 mV ( P < 0.05)] and BKCa and CaL current densities increased [BKCa: 2.54 ± 0.47 ( n = 11) vs. 1.12 ± 0.33 ( n = 12) pA/pF at +20 mV ( P < 0.05); CaL: −3.99 ± 0.53 ( n = 12) vs. −2.28 ± 0.20 ( n = 10) pA/pF at +20 mV ( P < 0.05)]. These findings support our hypothesis, and their impact on space cardiovascular research is discussed.

Primary and adaptive changes of A-type K+ currents in sympathetic neurons from hypertensive rats

1999 ◽  
Vol 276 (6) ◽  
pp. R1758-R1765 ◽  
Author(s):  
Walter P. Robertson ◽  
Geoffrey G. Schofield
Keyword(s):  
Current Density ◽  
Sympathetic Neurons ◽  
Activation Parameters ◽  
Cell Voltage ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Type K ◽  
Cervical Ganglion ◽  
Wistar Kyoto ◽  
Ganglion Neurons

The A-type K+ current ( I A) of superior cervical ganglion neurons acutely isolated from spontaneously hypertensive (SHR) and age-matched Wistar-Kyoto (WKY) rats was compared under whole cell voltage clamp. Activation parameters were similar in each strain. Steady-state inactivation was shifted approximately −6 mV in SHR, where one-half inactivation occurred at −81 mV vs. −75 mV in WKY rats. The shift was not present in prehypertensive SHR but remained in adult enalapril-treated SHR and, therefore, may represent a primary alteration of I A properties. I A amplitudes evoked from physiological potentials were similar, despite inactivation of a greater fraction of the current in the SHR. Comparing maximal I A densities revealed that current density is elevated in the SHR, which compensates for the inactivation shift. Current density decreased with age in WKY neurons but did not significantly decline in SHR neurons unless hypertension was prevented with enalapril. Thus adult SHR neurons may retain a high I Adensity as an adaptive response to offset potential hyperexcitability resulting from the hyperpolarized I A inactivation.

Acute renal denervation produces a diuresis and natriuresis in young SHR but not WKY rats

1986 ◽  
Vol 251 (4) ◽  
pp. F655-F661 ◽  
Author(s):  
M. A. Rudd ◽  
R. S. Grippo ◽  
W. J. Arendshorst
Keyword(s):  
Sodium Excretion ◽  
Renal Denervation ◽  
Strain Differences ◽  
Urine Flow ◽  
Sprague Dawley ◽  
Renal Vasculature ◽  
Renal Nerve ◽  
Water Excretion ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

Clearance experiments were conducted to determine the effect of acute unilateral renal denervation (DNX) on renal hemodynamics and salt and water excretion in anesthetized 6-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto genetic control rats (WKY). Before DNX, SHR had higher mean arterial pressure (33%) and renal vascular resistance (RVR) (57%) and lower glomerular filtration rate (GFR) (10%); urine flow and sodium excretion were similar. Following DNX in SHR, sodium and water excretion increased by 138 and 62%, respectively (P less than 0.001); GFR and RVR were unchanged. In contrast, DNX in WKY did not affect urine flow (0%) or sodium excretion (-21%). These strain differences were observed in Okamoto-Aoki rats from two sources. Effective DNX was indicated by 95% reduction of norepinephrine content 3 days after DNX in both strains. Six-week-old Sprague-Dawley and Munich-Wistar rats, in contrast to WKY, responded to DNX with a natriuresis (+182%) and diuresis (+95%) (P less than 0.001). Renal function was unaffected by sham DNX in SHR. Our results indicate that efferent renal nerve activity has little tonic influence on the renal vasculature in these young rats. Augmented neurotransmitter release and/or tubular responsiveness may be involved in fluid and electrolyte retention and the pathogenesis of hypertension in SHR. Conversely, blunted renal neuroeffector responses may prevent WKY from developing hypertension.

High-NaCl diets increase natriuretic and diuretic responses in salt-resistant but not salt-sensitive SHR

1991 ◽  
Vol 260 (6) ◽  
pp. F890-F897 ◽  
Author(s):  
M. S. Mozaffari ◽  
S. Jirakulsomchok ◽  
Z. H. Shao ◽  
J. M. Wyss
Keyword(s):  
Arterial Pressure ◽  
Renal Denervation ◽  
Isotonic Saline ◽  
Renal Nerves ◽  
Sprague Dawley ◽  
Volume Loading ◽  
Spontaneously Hypertensive ◽  
Volume Load ◽  
Sprague Dawley Rats ◽  
Wistar Kyoto

This study tested the hypothesis that NaCl-sensitive spontaneously hypertensive rats (SHR-S) display a defect in natriuretic and diuretic responses to acute volume loading that contributes to the rise in arterial pressure observed when the rats are fed a high-NaCl diet. Seven-week-old SHR-S and NaCl-resistant SHR rats (SHR-R) and normotensive (Wistar-Kyoto and Sprague-Dawley rats) were fed high- or basal NaCl diets. After 2.5 wk on the diets, preinstrumented conscious rats received an intravenous infusion (5% body wt; 0.5 ml/min) of isotonic saline, and urine was collected through a bladder catheter for 90 min. Control rats on the high-NaCl diet (compared with basal) excreted a significantly greater percentage of Na+ and volume load. In contrast, SHR-S on high-NaCl diet (compared with basal) had a very small increase in natriuretic response and no increase in diuretic response to volume expansion. The effect of renal denervation on natriuretic and diuretic responses to volume load was tested. In SHR-R on 1 and 8% NaCl diets, renal denervation had little or no effect on these responses, suggesting that renal nerves do not play a prominent role in the dietary NaCl-induced increases in the natriuretic and diuretic responses to volume load. These results demonstrate that NaCl-resistant rats rapidly adapt to diets high in NaCl content with increased natriuretic and diuretic responses to acute volume loading. The failure of SHR-S to adapt to the dietary challenge may result in volume loading and a secondary increase in arterial pressure after feeding.

Distribution of kallikrein-binding protein mRNA in kidneys and difference between SHR and WKY rats

1994 ◽  
Vol 267 (2) ◽  
pp. F325-F330 ◽  
Author(s):  
T. Yang ◽  
Y. Terada ◽  
H. Nonoguchi ◽  
M. Tsujino ◽  
K. Tomita ◽  
...  
Keyword(s):  
Blot Analysis ◽  
Binding Protein ◽  
Collecting Duct ◽  
Cortical Collecting Duct ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Sd Rats ◽  
Medullary Collecting Duct ◽  
Wistar Kyoto

We investigated kallikrein-binding protein (KBP) mRNA distribution in the kidney of Sprague-Dawley (SD) rats, spontaneously hypertensive rats (SHR), and Wistar-Kyoto strain (WKY) rats. Northern blot analysis revealed that KBP mRNA was located mainly in the medulla and with lower amounts in SHR than in WKY rats. KBP mRNA in microdissected nephron segments was detected by reverse transcription and polymerase chain reaction (RT-PCR) followed by Southern blot analysis. In SD rats, the most abundant signals were consistently found in inner medullary collecting duct (IMCD), with small amounts in outer medullary collecting duct, proximal convoluted tubule, and glomerulus. No signals were found in connecting tubule and cortical collecting duct. The nephron distribution of KBP mRNA was similar in WKY and SD rats. Only a small amount of signal was found, however, in IMCD of SHR. In conclusion, 1) KBP mRNA was predominantly distributed in the medullary segments of the distal nephron, downstream from the known kallikrein activity site in the collecting duct, and 2) KBP mRNA expression was significantly decreased in the kidney of SHR.

Dietary sodium restriction and development of hypertension in spontaneously hypertensive rats

1983 ◽  
Vol 245 (6) ◽  
pp. H1081-H1084 ◽  
Author(s):  
C. B. Toal ◽  
F. H. Leenen
Keyword(s):  
Blood Pressure ◽  
Control Diet ◽  
Dietary Sodium ◽  
Sodium Restriction ◽  
Spontaneously Hypertensive ◽  
Basal Blood Pressure ◽  
Blood Pressures ◽  
Dietary Sodium Restriction ◽  
Wistar Kyoto ◽  
And Control

Blood pressure and body weight of conscious spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were measured up to 16 wk of age in animals started at birth on five different sodium-containing diets. SHR on 9 mumol sodium/g food did not show a rise in basal blood pressure; however, when stressed the SHR still exhibited slightly higher blood pressures than WKY. In SHR on 17 mumol sodium/g food the development of hypertension was blunted compared with that of control (101 mumol/g) diet animals. SHR on 26 or 44 mumol sodium/g diet exhibited a development of hypertension similar to that of SHR on control diet. The 26 mumol/g, 44 mumol/g, and control sodium diet groups, regardless of strain, had similar growth rates. By contrast, on 17 mumol sodium/g food both SHR and WKY showed a substantially reduced growth rate, and all animals on 9 mumol sodium/g diet were severely retarded in growth. The results indicate that dietary sodium restriction can ameliorate the development of hypertension in SHR, but only when the sodium levels are so low as to affect overall growth.

Neurons from neonatal hypertensive rats exhibit abnormal membrane properties in vitro

1990 ◽  
Vol 259 (3) ◽  
pp. C389-C396 ◽  
Author(s):  
B. C. Jubelin ◽  
M. S. Kannan
Keyword(s):  
Action Potentials ◽  
Membrane Properties ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Enzymatic Dissociation ◽  
Sd Rats ◽  
High Calcium ◽  
Cervical Ganglia ◽  
Wistar Kyoto

The in vitro membrane properties of neurons from superior cervical ganglia (SCG) of neonatal spontaneously hypertensive (SH), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats were studied with microelectrodes. Neurons were obtained by enzymatic dissociation, plated, irradiated, and studied after 2-5 wk. Most SH neurons showed multiple action potentials in response to an intracellular long-duration depolarizing pulse (multiple firing), whereas most neurons from WKY or SD rats generated only one or two action potentials. Multiple firing was inhibited by low concentrations of cobalt (10(-5) M) but not by tetrodotoxin (TTX) (3 x 10(-6) M). Neither high calcium (5-10 x 10(-3) M) nor the Ca2+(-)channel opener BAY K 8644 (10(-6) M) could induce multiple firing in SD or WKY neurons. However, multiple firing was readily induced by apamin (10(-6) M) or tetraethylammonium chloride (5 x 10(-3) M) (Ca2+(-)activated K+(-)channels blockers), with cobalt and TTX sensitivities similar to native multiple-firing neurons. We conclude that 1) multiple firing is characteristic of neonate SH rats SCG neurons in vitro and depends on regenerative Ca2+ currents; 2) multiple firing in SH neurons results from a lack of activation of a Ca2+(-)activated K+ conductance and not from a lack of internal Ca2+ availability; and 3) multiple firing in SCG neurons mirrors a default in K+ conductance common to all cells in genetically hypertensive individuals.

IMPAIRMENT OF PLATELET PHOSPHOINOSITIDE METABOLISM IN PRIMARY HYPERTENSION

1987 ◽  
Author(s):  
S Koutouzov ◽  
A Remmal ◽  
P Marche ◽  
P Meyer
Keyword(s):  
Phospholipase C ◽  
Time Course ◽  
Blood Platelets ◽  
Second Messengers ◽  
Calcium Handling ◽  
Phosphoinositide Metabolism ◽  
Experimental Conditions ◽  
Spontaneously Hypertensive ◽  
Serotonin Secretion ◽  
Wistar Kyoto

Blood platelets from hypertensive patients and spontaneously hypertensive rats (SHR) display multiple abnormalities when compared with cells from normotensive controls. The major features of the modified platelet profile are an enhanced rate of adhesion/aggregation in response to many stimuli, a greater sensitivity for thrombin and adrenaline to produce increases in cytoplasmic free Ca2+, and an exaggerated release reaction. Furthermore, the resting levels of cytosolic free Ca2+ ions are specifically and constantly increased. Since phosphoinositides are involved in the stimulus-response coupling mediated by intracellular Ca2+ mobilization, the metabolism of these lipids was investigated in platelets of SHR and compared with those of normotensive Wistar-Kyoto rats (WKY). Following 32P-labelling of quiescent platelets, labeled lipids were analyzed both in platelets at rest and after thrombin stimulation. In resting platelets, the 32P associated with each of the phosphoinositides and phosphatidic acid (PA) was similar in SHR and WKY indicating that both the pool size of the various lipids and their basal turnover did not differ between the two strains. By contrast, within the first seconds after thrombin stimulation (10-60 sec), the dose-response and time-course curves of agonist-induced increase in 32P-PA were markedly shifted to the left and reached higher equilibrium levels in SHR. Since thrombin-induced 32P-PA formation is held as the most sensitive index of phospholipase C activity, our results indicate that this enzyme displays hyperreactivity in SHR (vs WKY). It is therefore likely that in SHR, the enhanced physiological responses (serotonin secretion, aggregation) that we observed under the same experimental conditions may be related to an increased formation of Phospholipase C products (inosi-toltriphosphate and diacylglycerol) which are the two second messengers responsible for internal Ca2+ mobilization and activation of protein kinase C, respectively. Therefore, these data suggest that the hypersensitivity of Phospholipase C may be involved in the overall alteration of cell calcium handling and hence in the SHR platelet responses.

Age-dependent overflow of endogenous norepinephrine from paraventricular hypothalamic nucleus of hypertensive rats

1993 ◽  
Vol 265 (1) ◽  
pp. H39-H46 ◽  
Author(s):  
J. M. Qualy ◽  
T. C. Westfall
Keyword(s):  
Blood Pressure ◽  
Neuronal Activity ◽  
Reciprocal Relationship ◽  
Hypothalamic Nucleus ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Paraventricular Hypothalamic Nucleus ◽  
Wistar Kyoto ◽  
The Relationship

The relationship between age and central noradrenergic neuronal activity of the paraventricular hypothalamic nucleus (PVH) was examined in 7- to 10-, 12- to 14-, and 30- to 36-wk-old Sprague-Dawley (SD), Wistar-Kyoto (WKY), and spontaneously hypertensive rats (SHR). As an index of noradrenergic activity, endogenous norepinephrine (NE) overflow was assessed utilizing a miniaturized push-pull cannula assembly in unanesthetized freely moving rats. NE overlow under basal, 56 mM K+ stimulation, and in response to pressor/depressor drugs, were examined in all three strains at all ages. Significant increases in basal and K(+)-stimulated overflow of endogenous NE from the PVH were observed in all ages of SHR compared with normotensive controls with the greatest percent increase occurring during the development of hypertension in SHR. In addition, a reciprocal relationship exists with respect to blood pressure and overflow of NE from the PVH such that increases/decreases in blood pressure elicit decreases/increases in NE overflow in all strains at all ages examined. However, developing hypertensive SHR exhibited attenuated decreases in overflow of NE from the PVH compared with age-matched controls and established hypertensive SHR. These results suggest that noradrenergic pathways of the PVH contribute to the development and maintenance of arterial pressure hemostasis and that enhanced central noradrenergic neuronal activity is greatest during the development of hypertension in SHR.

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