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.

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.

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

Adrenaline Neurons and PNMT Activity in the Brain and Spinal Cord of Genetically Hypertensive Rats and Rats with DOCA—salt Hypertension

1981 ◽  
Vol 61 (s7) ◽  
pp. 219s-221s ◽  
Author(s):  
J. P. Chalmers ◽  
P. R. C. Howe ◽  
Y. Wallmann ◽  
I. Tumuls
Keyword(s):  
Spinal Cord ◽  
Spontaneously Hypertensive Rat ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Genetically Hypertensive Rats ◽  
Salt Hypertension ◽  
Old Rats ◽  
Wistar Kyoto ◽  
Genetically Hypertensive

1. We have studied the number of phenylethanolamine-N-methyltransferase (PNMT)-containing nerve cells in the medulla and the activity of PNMT in the medulla, spinal cord and hypothalamus of the rat. 2. At 4 weeks of age there was an increase in the number of PNMT cells counted in the medulla of the spontaneously hypertensive rat (SHR; 21%, P < 0.01) and the stroke-prone spontaneously hypertensive rat (SHR-SP; 22%, P < 0.01) compared with the Wistar-Kyoto (WKY) control rat. 3. At 4 months of age there were no significant differences in the number of medullary PNMT cells in two normotensive strains (WKY and Fisher rats), two genetically hypertensive strains (SHR and SHR-SP) and in DOCA-salt hypertensive rats. 4. In four week old rats the activity of PNMT was increased by about 50% in the spinal cord and medulla of the SHR and SHR-SP compared with the WKY rats, and immunotitration experiments suggest that this is due to an increased concentration of enzyme. 5. At 4 months of age there were no increases in PNMT activity of either genetically hypertensive rats or DOCA-salt hypertensive rats.

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.

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.

scholarly journals Effects of dietary salt on angiotensin peptides in kidney.

1995 ◽  
Vol 6 (4) ◽  
pp. 1209-1215
Author(s):  
Q C Meng ◽  
J Durand ◽  
Y F Chen ◽  
S Oparil
Keyword(s):  
Angiotensin Ii ◽  
Spontaneously Hypertensive Rats ◽  
Spontaneously Hypertensive Rat ◽  
Sprague Dawley ◽  
Dietary Salt ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Angiotensin Peptides ◽  
Sprague Dawley Rats ◽  
Wistar Kyoto

This study used a novel simple method for the extraction, separation, identification, and quantitation of angiotensin-like immunoactivity from tissue to examine the effects of altering dietary NaCl intake on intrarenal angiotensin I, II, and III levels in salt-sensitive, spontaneously hypertensive rats, salt-resistant Wistar-Kyoto rats, and Sprague-Dawley rats. Seven-week-old male spontaneously hypertensive rats, Wistar-Kyoto rats, and Sprague-Dawley rats were assigned randomly to a diet containing either 8% (high) or 1% (basal) salt and were maintained on these diets for 3 wk. Rats were then decapitated without prior anesthesia, and kidneys were rapidly (< 30 s) removed, snap frozen in liquid nitrogen, and stored at -80 degrees C. Frozen tissue was extracted in 2 M acetic acid and then subjected to solid-phase extraction with the cation exchange resin AG 50W X4. Angiotensin peptides were separated by reversed-phase high-performance liquid chromatography on a phenyl silica gel column with an eluent consisting of 20% acetonitrile in 0.1 M ammonium phosphate buffer, pH 4.9, and quantitated by radioimmunoassay. The elution of standard peptides under isocratic conditions revealed clear resolution of angiotensin I, II, and III and the (1-7) and (3-8) peptides. Recoveries of both labeled and unlabeled angiotensin peptide standards from the extraction step were > 90%. Renal angiotensin II stores were significantly higher in spontaneously hypertensive rats than in Wistar-Kyoto or Sprague-Dawley rats, independent of diet. Renal angiotensin II and III were further suppressed during dietary salt supplementation in both salt-resistant strains but not in the spontaneously hypertensive rat. These findings are consistent with an enhanced (compared with Wistar-Kyoto and Sprague-Dawley rats) role for angiotensin II in the kidney of the salt-sensitive, spontaneously hypertensive rat, particularly under conditions of dietary salt supplementation.

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