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.

Vasodilation mediated by human PTH 1-34 in the spontaneously hypertensive rat

1984 ◽  
Vol 246 (1) ◽  
pp. F96-F100 ◽  
Author(s):  
D. A. McCarron ◽  
D. H. Ellison ◽  
S. Anderson
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Ionized Calcium ◽  
Experimental Hypertension ◽  
Base Line ◽  
Response Curves ◽  
Hypotensive Action ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Serum Ionized Calcium ◽  
Wistar Kyoto

Parathyroid hormone's cardiovascular effects were assessed in a model of experimental hypertension with known abnormalities of calcium metabolism. Mean arterial pressure (MAP) changes and serum ionized calcium responses were measured in the spontaneously hypertensive rat (SHR) and its normotensive control, the Wistar-Kyoto (WKY), following injections of synthetic human PTH 1-34. Six 22-wk-old SHR and six WKY were given intra-arterial serial injections (0.1-100 micrograms/kg) of hPTH 1-34. Both the SHR (P less than 0.001) and WKY (P less than 0.001) demonstrated log dose-dependent hypotensive responses that were maximal at 1 min, with recovery occurring between 15 and 30 min. The slopes, however, of the dose-response curves differed (P less than 0.01). The SHR experienced a greater maximal delta MAP [-93.7 +/- 2.4 (SHR) vs. -71.2 +/- 1.6 mmHg (WKY), P less than 0.01]. Furthermore, the duration of the hypotensive action of hPTH 1-34 was significantly longer (P less than 0.001) in the SHR. Even when corrected for base-line MAP the SHR demonstrated a significant (P = 0.025) enhancement of this vasodilator response at doses of 5 micrograms/kg and greater at time intervals between 3 and 9 min after injection. A transient decrease [2.25 +/- 0.10 (pre) vs. 2.17 +/- 0.11 meq/liter (1 min post), P less than 0.01] in serum ionized calcium occurred at 1 min. We conclude that hPTH 1-34 is a potent vasoactive peptide in both the normotensive WKY and the SHR. The greater maximal hypotensive response to hPTH 1-34 and the prolongation of this cardiovascular effect in the SHR may be an additional manifestation of this experimental animal's acknowledged abnormalities of cellular membrane calcium and phospholipid metabolism.

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.

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.

Age-dependent regulation of vasopressin V1a receptors in preglomerular vessels from the spontaneously hypertensive rat

2004 ◽  
Vol 286 (5) ◽  
pp. F997-F1003 ◽  
Author(s):  
Øyvind B. Vågnes ◽  
Frank H. Hansen ◽  
Rolf E. F. Christiansen ◽  
Camilla Gjerstad ◽  
Bjarne M. Iversen
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Mrna Level ◽  
Cytosolic Calcium ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Renal Vascular ◽  
Insight Into

Experiments were performed to get insight into the role of AVP receptor V1a regulation with age, i.e., during development and maintenance of high blood pressure. Previous studies showed an increased gene expression and renal vascular response to AVP in young spontaneously hypertensive rats (SHR). The age regulation of the V1a receptor was examined in preglomerular vessels from 5-, 10-, 20-, and 70-wk-old SHR using normotensive Wistar-Kyoto rats (WKY) as controls. Real-time PCR and ligand binding were used for analysis of receptor expression, and the change in cytosolic calcium concentration during stimulation of isolated preglomerular vessels with AVP was studied. Studies showed an increase of the V1a receptor protein and mRNA from 5-and 10-wk-old SHR compared with vessels from 20- and 70-wk-old SHR. In 5-wk-old SHR receptor density was 84 ± 13 fmol/mg protein, and 38 ± 11 fmol/mg protein in 70-wk-old SHR ( P < 0.05). mRNA in the 5- and 70-wk-old SHR was 15,854 ± 629 and 3,181 ± 224 V1a mRNA/108 18S ribosomal RNA, respectively ( P < 0.001). Values from WKY at all ages were similar to 20- and 70-wk-old SHR. During stimulation with AVP, the change in cytosolic calcium in vessels from 5-wk-old SHR increased 234 ± 59 nM, whereas the increase was 89 ± 9 nM in 70-wk-old SHR ( P = 0.03). These results indicate that the V1a receptor is increased at protein and mRNA level during development of hypertension in SHR but is normalized when hypertension is established.

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.

Enhanced response of arterioles to oxygen during development of hypertension in SHR

1986 ◽  
Vol 250 (5) ◽  
pp. H761-H764 ◽  
Author(s):  
J. H. Lombard ◽  
M. E. Hess ◽  
W. J. Stekiel
Keyword(s):  
Skeletal Muscle ◽  
Vascular Resistance ◽  
Local Control ◽  
Fourth Order ◽  
Spontaneously Hypertensive Rat ◽  
Control Mechanisms ◽  
Cremaster Muscle ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

The goal of this study was to assess the possible role of O2-related local control mechanisms in contributing to an elevated skeletal muscle resistance during the development of hypertension in the spontaneously hypertensive rat (SHR). Diameters of first- (1A), second- (2A), third- (3A), and fourth-order (4A) arterioles were measured by television microscopy in the cremaster muscle of SHR in the early (4- to 6-wk-old) and rapidly developing (8- to 9-wk-old) stages of hypertension and in age-matched normotensive Wistar-Kyoto (WKY) controls. Active neurogenic tone was blocked by superfusing the tissue with 0.1 microgram/ml tetrodotoxin. When superfusion solution PO2 was elevated by changing the gas equilibration mixture from 0 to 5% O2, neurally blocked 3A and 4A of SHR exhibited a significantly greater constriction and a higher incidence of complete closure than those of their age-matched WKY controls. However, there were no significant differences in the constriction of larger arterioles (1A and 2A) in response to elevated superfusion solution PO2. The results suggest that O2-related local control mechanisms could contribute to constriction and closure of small arterioles and to an elevated skeletal muscle vascular resistance early in the development of hypertension in SHR

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