scholarly journals Posttranslational mechanisms associated with reduced NHE3 activity in adult vs. young prehypertensive SHR

2010 ◽  
Vol 299 (4) ◽  
pp. F872-F881 ◽  
Author(s):  
Renato O. Crajoinas ◽  
Lucília M. A. Lessa ◽  
Luciene R. Carraro-Lacroix ◽  
Ana Paula C. Davel ◽  
Bruna P. M. Pacheco ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Spontaneously Hypertensive Rat ◽  
The Body ◽  
Sodium Reabsorption ◽  
Spontaneously Hypertensive ◽  
Bicarbonate Reabsorption ◽  
Before And After ◽  
Wistar Kyoto ◽  
Lower Ratio

Abnormalities in renal proximal tubular (PT) sodium transport play an important role in the pathophysiology of essential hypertension. The Na+/H+ exchanger isoform 3 (NHE3) represents the major route for sodium entry across the apical membrane of renal PT cells. We therefore aimed to assess in vivo NHE3 transport activity and to define the molecular mechanisms underlying NHE3 regulation before and after development of hypertension in the spontaneously hypertensive rat (SHR). NHE3 function was measured as the rate of bicarbonate reabsorption by means of in vivo stationary microperfusion in PT from young prehypertensive SHR (Y-SHR; 5-wk-old), adult SHR (A-SHR; 14-wk-old), and age-matched Wistar Kyoto (WKY) rats. We found that NHE3-mediated PT bicarbonate reabsorption was reduced with age in the SHR (1.08 ± 0.10 vs. 0.41 ± 0.04 nmol/cm2×s), while it was increased in the transition from youth to adulthood in the WKY rat (0.59 ± 0.05 vs. 1.26 ± 0.11 nmol/cm2×s). Higher NHE3 activity in the Y-SHR compared with A-SHR was associated with a predominant microvilli confinement and a lower ratio of phosphorylated NHE3 at serine-552 to total NHE3 (P-NHE3/total). After development of hypertension, P-NHE3/total increased and NHE3 was retracted out of the microvillar microdomain along with the regulator dipeptidyl peptidase IV (DPPIV). Collectively, our data suggest that the PT is playing a role in adapting to the hypertension in the SHR. The molecular mechanisms of this adaptation possibly include an increase of P-NHE3/total and a redistribution of the NHE3-DPPIV complex from the body to the base of the PT microvilli, both predicted to decrease sodium reabsorption.

Transport of calcium by duodenum of spontaneously hypertensive rat

1981 ◽  
Vol 241 (4) ◽  
pp. G344-G347 ◽  
Author(s):  
M. A. Toraason ◽  
G. L. Wright
Keyword(s):  
Calcium Transport ◽  
Spontaneously Hypertensive Rat ◽  
Detectable Effect ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Before And After ◽  
Rat Strain ◽  
Wistar Kyoto

The absorption of calcium by segments of duodenum obtained from spontaneously hypertensive (SH) rats and normotensive Wistar-Kyoto (WKy) rats was measured before and after the development of hypertension. The systolic blood pressure (SBP) of 5-wk-old SH rats (116 +/- 4 Torr) was significantly elevated above that of age-matched WKy rats (103 +/- 3 Torr) but was not at a level generally considered to be hypertensive. Values obtained for calcium transport [ratio of serosal-to-mucosal fluid 45Ca2+ concn (S/M ratio)] from everted duodenal sacs were similar between the two groups at this age. At 12 wk of age, SH rats exhibited a SBP (153 +/- 4 Torr) well above that of WKy controls (127 +/- 3 Torr), and calcium S/M ratios for duodenal sacs were significantly greater than the WKy control values. Similarly, the in vivo uptake of calcium in duodenal segments was significantly elevated in 12-wk-old SH rats compared with WKy controls. The administration of vitamin D3 or its metabolite, 25-hydroxycholecalciferol, had no detectable effect on duodenal transport of calcium in 12-wk-old SH or WKy rats. By comparison, 1,25-dihydroxycholecalciferol produced a significant increase in duodenal calcium transport both in vitro and in vivo in WKy but not in SH rats. The results indicate a distinct abnormality in the transport of calcium in the duodenum of SH rats, suggesting that the decrease in duodenal uptake of calcium that normally occurs with maturation is slow to develop in this rat strain.

Role of adenosine in noradrenergic neurotransmission in spontaneously hypertensive rats

1987 ◽  
Vol 253 (4) ◽  
pp. H909-H918 ◽  
Author(s):  
E. K. Jackson
Keyword(s):  
Plasma Levels ◽  
Spontaneously Hypertensive Rat ◽  
Base Line ◽  
Inhibitory Effects ◽  
Spontaneously Hypertensive ◽  
Vascular Responses ◽  
Rat Mesentery ◽  
Wistar Kyoto

The purpose of this study was to compare the in vivo role of adenosine as a modulator of noradrenergic neurotransmission in the spontaneously hypertensive rat (SHR) and Wistar-Kyoto control rat (WKY). In the in situ blood-perfused rat mesentery, vascular responses to periarterial (sympathetic) nerve stimulation (PNS) and to exogenous norepinephrine (NE) were enhanced in SHR compared with WKY. In both SHR and WKY, vascular responses to PNS were more sensitive to inhibition by adenosine than were responses to NE. At matched base-line vascular responses, compared with WKY, SHR were less sensitive to the inhibitory effects of adenosine on vascular responses to PNS, but SHR and WKY were equally sensitive with respect to adenosine-induced inhibition of responses to NE. Antagonism of adenosine receptors with 1,3-dipropyl-8-p-sulfophenylxanthine shifted the dose-response curve to exogenous adenosine sixfold to the right yet did not influence vascular responses to PNS or NE in either SHR or WKY. Furthermore, PNS did not alter either arterial or mesenteric venous plasma levels of adenosine in SHR or WKY, and plasma levels of adenosine in both strains were always lower than the calculated threshold level required to attenuate neurotransmission. It is concluded that in vivo 1) exogenous adenosine interferes with noradrenergic neurotransmission in both SHR and WKY; 2) SHR are less sensitive to the inhibitory effects of exogenous adenosine on noradrenergic neurotransmission than are WKY; 3) endogenous adenosine does not play a role in modulating neurotransmission in either strain under the conditions of this study; and 4) enhanced noradrenergic neurotransmission in the SHR is not due to defective modulation of neurotransmission by adenosine.

Mechanism of exaggerated diuresis in spontaneously hypertensive rats

1978 ◽  
Vol 235 (5) ◽  
pp. F409-F416 ◽  
Author(s):  
Gerald F. DiBona ◽  
Linda L. Rios
Keyword(s):  
Volume Expansion ◽  
Spontaneously Hypertensive Rats ◽  
Spontaneously Hypertensive Rat ◽  
Renal Perfusion ◽  
Sodium Reabsorption ◽  
Loop Of Henle ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Single Nephron ◽  
Wistar Kyoto

The mechanism of exaggerated diuresis and natriuresis was studied in spontaneously hypertensive rats (SHR) by renal clearance and micropuncture techniques. Control normotensive rats of the same age and sex [Wistar-Kyoto rats (WKY)] were also studied. During the hydropenic control and the volume-expansion experimental periods absolute and fractional water and sodium excretion were greater in SHR than in WKY. Although fractional and absolute water and sodium reabsorption were similar along the proximal convolution in SHR and WKY, fractional and absolute water reabsorption in Henle's loop was less in SHR than in WKY. Hydrostatic and colloid osmotic pressures in the cortical peritubular microvasculature were similar in WKY and SHR. Acute normalization of renal perfusion pressure by aortic constriction reversed the exaggerated diuresis and natriuresis in SHR by halving the filtered load of water and sodium; whole kidney and single nephron glomerular filtration rates and blood flows decreased by 50%. It is concluded that the exaggerated diuresis and natriuresis of the spontaneously hypertensive rat is caused by a decreased reabsorption in the loop of Henle. The mechanism of this decreased reabsorption in the loop of Henle cannot be explained by alterations in the measured physical forces in the renal cortical microvasculature. natriuresis; autoregulation; volume expansion Submitted on November 15, 1977 Accepted on June 7, 1978

Intestinal calcium transport in the spontaneously hypertensive rat: response to calcium depletion

1986 ◽  
Vol 250 (4) ◽  
pp. G412-G419
Author(s):  
H. P. Schedl ◽  
D. L. Miller ◽  
R. L. Horst ◽  
H. D. Wilson ◽  
K. Natarajan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Small Intestine ◽  
Calcium Transport ◽  
Spontaneously Hypertensive Rat ◽  
Calcium Depletion ◽  
Spontaneously Hypertensive ◽  
Distal Small Intestine ◽  
Wistar Kyoto

We previously found intestinal Ca2+ transport to be lower in the spontaneously hypertensive (SH) as compared with the Wistar-Kyoto control (WKY) rat. These animals were fed a relatively high (1%) Ca2+ diet, and the concentration of 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3] in serum was the same in both groups. In the present experiment we tested the possibility that the lower Ca2+ transport in the SH rat was the result of unresponsiveness to 1 alpha,25(OH)2D3. We fed diets high and low in Ca2+ and measured serum 1 alpha,25(OH)2D3 and Ca2+ transport. Serum 1 alpha,25(OH)2D3 increased in response to Ca2+ depletion at both 5 and 12 wk in both the WKY and SH rat. With high-Ca2+ diet, Ca2+ transport was lower in SH than in WKY when studied 1) in vitro in duodenum at 5 wk of age, and 2) in vivo in proximal and distal small intestine at 12 wk of age. Ca2+ transport increased in SH in response to Ca2+ depletion, but not in WKY, except in distal small intestine in vivo at 12 wk. In summary, although Ca2+ transport is lower in the SH as compared with the WKY rat when vitamin D activity is basal through feeding a high-Ca2+ diet, Ca2+ transport increases in the SH rat in response to the increase in 1 alpha,25(OH)2D3 produced by feeding a low-Ca2+ diet. We conclude that 1) the vitamin D-regulated component of mediated Ca2+ transport is intact in the SH rat and is unrelated to hypertension, and 2) mediated Ca2+ transport under basal conditions, i.e., nonvitamin D-regulated, differs in the SH and WKY rats and may be related to hypertension.

scholarly journals Cardiac sympathetic dysfunction in the prehypertensive spontaneously hypertensive rat

2013 ◽  
Vol 305 (7) ◽  
pp. H980-H986 ◽  
Author(s):  
Julia Shanks ◽  
Sotiria Manou-Stathopoulou ◽  
Chieh-Ju Lu ◽  
Dan Li ◽  
David J. Paterson ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Calcium Transients ◽  
Vagus Stimulation ◽  
Spontaneously Hypertensive ◽  
Sympathetic Dysfunction ◽  
The Difference ◽  
Wistar Kyoto ◽  
The Right ◽  
Right Atria

Recent studies in prehypertensive spontaneously hypertensive rats (SHR) have shown larger calcium transients and reduced norepinephrine transporter (NET) activity in cultured stellate neurons compared with Wistar-Kyoto (WKY) controls, although the functional significance of these results is unknown. We hypothesized that peripheral sympathetic responsiveness in the SHR at 4 wk of age would be exaggerated compared with the WKY. In vivo arterial pressure (under 2% isoflurane) was similar in SHRs (88 ± 2/50 ± 3 mmHg, n = 18) compared with WKYs (88 ± 3/49 ± 4 mmHg, n = 20). However, a small but significant ( P < 0.05) tachycardia was observed in the young SHR despite the heart rate response to vagus stimulation (3 and 5 Hz) in vivo being similar (SHR: n = 12, WKY: n = 10). In isolated atrial preparations there was a significantly greater tachycardia during right stellate stimulation (5 and 7 Hz) in SHRs ( n = 19) compared with WKYs ( n = 16) but not in response to exogenous NE (0.025–5 μM, SHR: n = 10, WKY: n = 10). There was also a significantly greater release of [3H]NE to field stimulation (5 Hz) of atria in the SHR (SHR: n = 17, WKY: n = 16). Additionally, plasma levels of neuropeptide Y sampled from the right atria in vivo were also higher in the SHR (ELISA, n = 12 for both groups). The difference in [3H]NE release between SHR and WKY could be normalized by the NET inhibitor desipramine (1 μM, SHR: n = 10, WKY: n = 8) but not the α2-receptor antagonist yohimbine (1 μM, SHR: n = 7, WKY: n = 8). Increased cardiac sympathetic neurotransmission driven by larger neuronal calcium transients and reduced NE reuptake translates into enhanced cardiac sympathetic responsiveness at the end organ in prehypertensive SHRs.

Enhanced response to AVP in the interlobular artery from the spontaneously hypertensive rat

2005 ◽  
Vol 288 (5) ◽  
pp. F1023-F1031 ◽  
Author(s):  
Frank H. Hansen ◽  
Øyvind B. Vågnes ◽  
Bjarne M. Iversen
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Free Calcium ◽  
Ratio Increase ◽  
Spontaneously Hypertensive ◽  
Relative Contribution ◽  
Afferent Arterioles ◽  
Wistar Kyoto ◽  
Sustained Responses ◽  
External Calcium

Arginine vasopressin (AVP) induces exaggerated intracellular free calcium (Cai2+) responses in preglomerular smooth muscle cells from young spontaneously hypertensive rats (SHR) due to increased density of the AVP V1a receptor. The intention of the present paper was to examine the relative contribution of afferent arterioles (AA) and interlobular artery (ILA) in AVP- and norepinephrine-induced calcium signaling. The kidneys were perfused with agar solution in vivo, and thin cortical slices were enzyme digested to produce isolated agar-filled vascular fragments. Calcium responses were recorded in fura 2-loaded cells by Ca2+ imaging. Diameter changes were measured after AVP stimulation and mRNA for V1a was measured on isolated vessel fragments. SHR had a significantly higher baseline calcium ratio and lower resting diameter compared with normotensive Wistar-Kyoto rats (WKY). Stimulation with AVP (10−7 M) in ILA fragments from SHR induced a ratio increase of 0.49 ± 0.09, significantly higher than the ratio increase in AA from SHR (0.20 ± 0.03, P < 0.01) and in ILA from WKY (0.24 ± 0.03, P < 0.01). Stimulation with norepinephrine (10−7 M) induced responses homogeneously distributed between the segments and strains. Nifedipine treatment or removal of external calcium (Cao2+) reduced the norepinephrine-induced peak response. Both norepinephrine- and AVP-induced sustained responses were abolished after Cao2+ removal in SHR and WKY ( P < 0.01). Measurements of V1a receptor mRNA on isolated segments showed a threefold increase in ILA from SHR. The present findings indicate that the exaggerated Ca2+ and contractile response to AVP in SHR is mainly mediated through ILA vasoconstriction.

Renal Prostaglandin Production in the Japanese (Kyoto) Spontaneously Hypertensive Rat

1978 ◽  
Vol 55 (s4) ◽  
pp. 191s-193s ◽  
Author(s):  
Michael J. Dunn
Keyword(s):  
Prostaglandin E2 ◽  
Spontaneously Hypertensive Rat ◽  
Rat Kidney ◽  
Prostaglandin F2α ◽  
Spontaneously Hypertensive ◽  
Prostaglandin Production ◽  
Show Evidence ◽  
Wistar Kyoto ◽  
Venous Plasma

1. Renal venous and urinary prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) were measured in spontaneously hypertensive (SH) rats and Wistar-Kyoto normotensive rats (WKy) of 4 different ages, ranging from 4 to 54 weeks. 2. Renal venous (plasma) PGE2 and PGF2α were similar in WKy and SH rats at all ages, except for greater PGF2α in 40–54 week old SH rats. 3. Urinary (24 h) PGE2 and PGF2α were similar in WKy and SH rats at all ages, except for greater PGE2 in 7–12 week old SH rats. 4. There was a significant trend for renal venous and urinary PGE2 and PGF2α to decrease with advancing age. 5. These experiments did not show evidence that the SH rat kidney, in vivo, has an abnormality of PGE2 or PGF2α production or degradation, which alters secretion or excretion of either prostaglandin.

Depressor effect of diabetes in the spontaneously hypertensive rat: associated changes in heart performance

1986 ◽  
Vol 64 (9) ◽  
pp. 1177-1184 ◽  
Author(s):  
Robert L. Rodgers
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Systolic Arterial Pressure ◽  
Left Ventricular ◽  
Stroke Work ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Rat Hearts ◽  
Heart Size ◽  
Wistar Kyoto

Effects of streptozotocin-induced diabetes (8 weeks) on the performance of perfused hearts from spontaneously hypertensive (SH) rats were compared with effects on normotensive Wistar–Kyoto (WK) and Sprague–Dawley (SD) rat hearts. Diabetes markedly decreased systolic arterial pressure (SAP) of SH rats in vivo but did not affect SAP of either of the normotensive strains. Diabetes also reduced heart size of SH and normotensive rats and reversed absolute left ventricular hypertrophy (wall-to-lumen ratios and left-to-right ventricular weight ratios) of SH rats. Heart perfusion at the end of the 8-week period revealed that diabetes (i) reduced hydraulic work at high pressure loads and efficiency of contraction (work/μ.LO2 consumed) of SH rat hearts but not of WK or SD hearts, and (ii) depressed left ventricular pulse pressure development (LVPP) and contractility (LV + dP/dt) of SH hearts more extensively than it reduced these variables in either of the normotensive control groups. Effects of diabetes which were similar in hypertensive and normotensive hearts were reductions in stroke work at high volume loads and depressions in LV−dP/dt. Attendant hypothyroidism probably contributed to the reductions in SAP, heart size, LVPP, LV+ and −dP/dt, and stroke work but not to the decreased efficiency or reversal of hypertrophy of SH rat hearts. Malnutrition of SH rats, like hypothyroidism, also decreased heart size without reversing hypertrophy but had no effect on SAP and only reduced LV−dP/dt. The results show that diabetes reversed hypertrophy and selectively reduced contraction efficiency, contractility, and LVPP of SH hearts, but otherwise the effects of diabetes in hypertensive and normotensive rat strains were similar to each other. The possible contribution of hypothyroidism to the observed effects of diabetes in SH rats remains to be clarified.

scholarly journals Cardiac phenylethanolamine N-methyltransferase: localization and regulation of gene expression in the spontaneously hypertensive rat

2016 ◽  
Vol 94 (4) ◽  
pp. 363-372 ◽  
Author(s):  
Heather Peltsch ◽  
Sandhya Khurana ◽  
Collin J. Byrne ◽  
Phong Nguyen ◽  
Neelam Khaper ◽  
...  
Keyword(s):  
Right Atrium ◽  
Molecular Mechanisms ◽  
Genetic Model ◽  
Spontaneously Hypertensive Rat ◽  
Regulation Of Gene Expression ◽  
Transcriptional Regulators ◽  
Spontaneously Hypertensive ◽  
Protein Levels ◽  
Wistar Kyoto ◽  
The Right

Phenylethanolamine N-methyltransferase (PNMT) is the terminal enzyme in the catecholamine biosynthetic pathway responsible for adrenaline biosynthesis. Adrenaline is involved in the sympathetic control of blood pressure; it augments cardiac function by increasing stroke volume and cardiac output. Genetic mapping studies have linked the PNMT gene to hypertension. This study examined the expression of cardiac PNMT and changes in its transcriptional regulators in the spontaneously hypertensive (SHR) and wild type Wistar-Kyoto (WKY) rats. SHR exhibit elevated levels of corticosterone, and lower levels of the cytokine IL-1β, revealing systemic differences between SHR and WKY. PNMT mRNA was significantly increased in all chambers of the heart in the SHR, with the greatest increase in the right atrium. Transcriptional regulators of the PNMT promoter show elevated expression of Egr-1, Sp1, AP-2, and GR mRNA in all chambers of the SHR heart, while protein levels of Sp1, Egr-1, and GR were elevated only in the right atrium. Interestingly, only AP-2 protein-DNA binding was increased, suggesting it may be a key regulator of cardiac PNMT in SHR. This study provides the first insights into the molecular mechanisms involved in the dysregulation of cardiac PNMT in a genetic model of hypertension.

scholarly journals Chronic NO Restriction in Hypertensive Rats Increases Abdominal but Not Thoracic Aortic Intrinsic Stiffness via an Augmentation in Profibrotic Materials

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
George Lindesay ◽  
Yvonnick Bézie ◽  
Christophe Ragonnet ◽  
Véronique Duchatelle ◽  
Marc Isabelle ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rat ◽  
Dynamic Properties ◽  
Stiffness Index ◽  
Operating Pressure ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Spontaneously Hypertensive Rat Model

The spontaneously hypertensive rat model with reduced NO synthesis (SHRLN) shares features with aging and hypertension in humans, among other a severe aortic stiffening. The present in vivo study aimed to compare thoracic (TA) and abdominal (AA) aortic stiffness in the SHRLN (treated 5 weeks with L-NAME), SHR, and normotensive Wistar Kyoto (WKY). Dynamic properties of TA and AA were measured in the same rats, using echotracking recording of aortic diameter coupled with blood pressure (BP). Measurements were performed first at operating BP and then after BP reduction in hypertensive rats, thus in isobaric conditions. Histological staining and immunohistochemistry were used for structural analysis at both sites. At operating pressure, BP and pulse pressure (PP) were higher in SHRLN compared with SHR. Stiffness index was also increased and distensibility decreased in both TA and AA in SHRLN. At WKY-matched blood pressure, isobaric AA parameters remained specifically altered in SHRLN, whereas TA recovered to values identical to WKYs. Collagen, fibronectin, α5-selectin, and FAK were increased in SHRLN compared with SHR or WKY. Nevertheless, only the strong accumulations of fibronectin and collagen at the AA site in SHRLN were associated with intrinsic stiffening. In conclusion, we confirm that NO restriction associated with hypertension induces a severe pathological phenotype and shows that L-NAME induced stiffening is more pronounced in AA than in TA as a result of greater fibrosis.

Sign in / Sign up

Export Citation Format

Share Document