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.

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.

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.

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.

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 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.

Development of microvascular rarefaction in the spontaneously hypertensive rat

1982 ◽  
Vol 243 (2) ◽  
pp. H243-H251 ◽  
Author(s):  
R. L. Prewitt ◽  
I. I. Chen ◽  
R. Dowell
Keyword(s):  
Elevated Level ◽  
Spontaneously Hypertensive Rat ◽  
Capillary Density ◽  
Gracilis Muscle ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Arteriolar Wall ◽  
Wistar Kyoto ◽  
Microvascular Rarefaction

Using stereological methods in vivo, we have investigated the rarefaction of arterioles and capillaries in male spontaneously hypertensive rats (SHR) and the Wistar-Kyoto controls (WKY) at 6-8, 12-14, and 16-18 wk of age. Under chloralose-urethan anesthesia, the gracilis muscle was isolated for microscopic observation. Vessel length and surface area per unit volume of tissue (density) were determined during three consecutive states: innervation, denervation, and vasodilation with nitroprusside. Arteriolar wall-to-lumen ratio was measured after vasodilation. At 6-8 wk capillary density was reduced in the SHR. At 12-14 wk there was a reduction of arteriole and capillary density under innervated and denervated conditions but not after vasodilation (a state of functional rarefaction). At 16-18 wk there was a reduction of arteriolar and capillary density under all three conditions (a state of anatomical rarefaction). At 12-14 and 16-18 wk there was an elevated level of arteriolar vasoconstriction in the SHR that was masked in any one state by the closure of the smaller arterioles. Arteriolar wall-to-lumen ratio was not elevated in the SHR at any time. Arteriolar closure was not reversed by acute denervation.

Norepinephrine-induced calcium signaling pathways in afferent arterioles of genetically hypertensive rats

2001 ◽  
Vol 281 (2) ◽  
pp. F264-F272 ◽  
Author(s):  
Max Salomonsson ◽  
William J. Arendshorst
Keyword(s):  
Strain Difference ◽  
Strain Differences ◽  
External Solution ◽  
Free Calcium ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Free Calcium Concentration ◽  
Afferent Arterioles ◽  
Wistar Kyoto ◽  
A Site

This study provides new information about the relative importance of calcium mobilization and entry in the renal vascular response to adrenoceptor activation in afferent arterioles isolated from 7- to 8-wk-old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Intracellular free calcium concentration ([Ca2+]i) was measured in microdissected arterioles utilizing ratiometric photometry of fura 2 fluorescence. There was no significant strain difference in baseline [Ca2+]i. Norepinephrine (NE; 10−6 and 10−7 M) elicited immediate, sustained increases in [Ca2+]i. The general temporal pattern of response to 10−6 M NE consisted of an initial peak and a maintained plateau phase. The response to NE was partially blocked by nifedipine (10−6 M) or 8-( N,N-diethylamino) octyl-3,4,5-trimetoxybenzoate (TMB-8; 10−5 M). A calcium-free external solution abolished the sustained [Ca2+]i plateau response to NE, with less influence on the peak response. In the absence of calcium entry, TMB-8 (10−5 M) completely blocked the calcium response to NE in WKY but not SHR, suggesting strain differences in mobilization. A higher concentration of TMB-8 (10−4 M), however, blocked all discernible mobilization in both strains. We conclude that there are differences in Ca2+ handling in renal resistance vessels between young WKY and SHR with respect to mobilization stimulated by α-adrenoceptors. Afferent arterioles of young SHR appear to have a larger inositol-1,4,5-trisphosphate-sensitive pool or release from a site less accessible to TMB-8.

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