scholarly journals Chronic Dantrolene Treatment Does Not Affect Hypertension, but Attenuates Sympathetic Stimulation Enhanced Atrial Fibrillation Inducibility in SHR

2020 ◽  
Vol 33 (5) ◽  
pp. 407-413 ◽  
Author(s):  
Jae S Lee ◽  
Lisa Greco ◽  
Allan Migirov ◽  
Ying Li ◽  
A Martin Gerdes ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Experimental Period ◽  
Vehicle Group ◽  
Sympathetic Stimulation ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Blood Pressures ◽  
Wistar Kyoto ◽  
Hypertension Development

Abstract Background Ryanodine receptor (RyR) dysfunction in skeletal muscle (RyR1) leads to malignant hyperthermia, and in cardiac muscle (RyR2) triggers cardiac arrhythmias. We hypothesized that RyR dysfunction in vascular smooth muscle could increase vascular resistance and hypertension, and may contribute to increased atrial fibrillation (AF) in hypertension. Thus, stabilizing RyR function with chronic dantrolene treatment may attenuate hypertension and AF inducibility in spontaneously hypertensive rats (SHR). Methods Male SHR (16 weeks old) were randomized into vehicle- (n = 10) and dantrolene-treated (10 mg/kg/day, n = 10) groups for 4 weeks. Wistar Kyoto (WKY, n = 11) rats served as controls. Blood pressures (BP) were monitored before and during the 4-week treatment. After 4-week treatment, direct BP, echocardiography, and hemodynamics were recorded. AF inducibility tests were performed in vivo at baseline and repeated under sympathetic stimulation (SS). Results Compared with WKY, SHR had significantly higher BP throughout the experimental period. Dantrolene treatment had no effect on BP levels in SHR (final systolic BP 212 ± 9 mm Hg in vehicle group vs. 208 ± 16 mm Hg in dantrolene group, P > 0.05). AF inducibility was very low and not significantly different between 5-month-old WKY and SHR at baseline. However, under SS, AF inducibility and duration were significantly increased in SHR (20% in WKY vs. 60% in SHR-vehicle, P<0.05). Dantrolene treatment significantly attenuated AF inducibility under SS in SHR (60% in vehicle vs. 20% in dantrolene, P < 0.05). Conclusions Stabilizing RyR with chronic dantrolene treatment does not affect hypertension development in SHR. SHR has increased vulnerability to AF induction under SS, which can be attenuated with dantrolene treatment.

scholarly journals Dehulled Adlay Consumption Modulates Blood Pressure in Spontaneously Hypertensive Rats and Overweight and Obese Young Adults

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2305
Author(s):  
Wan-Ju Yeh ◽  
Jung Ko ◽  
Wei-Yi Cheng ◽  
Hsin-Yi Yang
Keyword(s):  
Blood Pressure ◽  
Daily Intake ◽  
Experimental Period ◽  
Overweight And Obesity ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Beneficial Effects ◽  
Underlying Mechanisms ◽  
Grain Foods

High blood pressure is a crucial risk factor for many cardiovascular diseases, and a diet rich in whole-grain foods may modulate blood pressure. This study investigated the effects of dehulled adlay consumption on blood pressure in vivo. We initially fed spontaneous hypertensive rats diets without (SHR group) or with 12 or 24% dehulled adlay (SHR + LA and SHR + HA groups), and discovered that it could limit blood pressure increases over a 12-week experimental period. Although we found no significant changes in plasma, heart, and kidney angiotensin-converting enzyme activities, both adlay-consuming groups had lower endothelin-1 and creatinine concentrations than the SHR group; the SHR + HA group also had lower aspartate aminotransferase and uric acid levels than the SHR group did. We later recruited 23 participants with overweight and obesity, and they consumed 60 g of dehulled adlay daily for a six-week experimental period. At the end of the study, we observed a significant decrease in the group’s systolic blood pressure (SBP), and the change in SBP was even more evident in participants with high baseline SBP. In conclusion, our results suggested that daily intake of dehulled adlay had beneficial effects in blood-pressure management. Future studies may further clarify the possible underlying mechanisms for the consuming of dehulled adlay as a beneficial dietary approach for people at risk of hypertension.

scholarly journals Duration of Electrically Induced Atrial Fibrillation Is Augmented by High Voltage of Stimulus with Higher Blood Pressure in Hypertensive Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Tomomi Nagayama ◽  
Yoshitaka Hirooka ◽  
Akiko Chishaki ◽  
Masao Takemoto ◽  
Yasushi Mukai ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Arterial Pressure ◽  
High Voltage ◽  
Spontaneously Hypertensive Rats ◽  
Low Voltage ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
High Stimulus ◽  
Wistar Kyoto

Objective.Many previous clinical studies have suggested that atrial fibrillation (AF) is closely associated with hypertension. However, the benefits of antihypertensive therapy on AF are still inconsistent, and it is necessary to explore the factors augmenting AF in hypertensive rats. The aim of the present study was to investigate the correlation between arterial pressure or voltage stimulus and to the duration of electrically induced AF in normotensive or hypertensive rats.Methods.AF was reproducibly induced by transesophageal atrial burst pacing in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). We did the burst pacing at high (20 V) or low (5 V) voltage.Results.Duration of AF did not correlate with systolic blood pressure (SBP) and stimulus voltage in WKY. However, only in SHR, duration of AF with high stimulus voltage significantly correlated with SBP and was significantly longer in high than in low voltage stimulus.Discussion and Conclusion.Duration of AF is augmented by high voltage stimulus with higher blood pressure in SHR.

Primary versus secondary structural changes of the blood vessels in hypertension

1985 ◽  
Vol 63 (4) ◽  
pp. 392-401 ◽  
Author(s):  
Robert M. K. W. Lee ◽  
John S. Smeda
Keyword(s):  
Blood Pressure ◽  
Blood Vessels ◽  
Structural Changes ◽  
Vascular Wall ◽  
Wall Thickening ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Pressure Independent ◽  
Hypertension Development

Various researchers have hypothesized that the thickening of the vascular wall plays an important role in the maintenance of hypertension. Such an alteration can increase the vascular resistance by exerting two effects. A thickened vascular wall could occlude the lumen of the blood vessel and (or) cause the artery to hyperreact to contractile stimuli. Until recently, it has been a general conclusion that such alterations were a secondary adaptation produced by the elevation of blood pressure. Consistent with this view, certain classes of larger arteries do exhibit a thickened vascular wall late during hypertension development and such changes can be prevented from occurring by antihypertensive treatment. However, recent studies involving the mesenteric and renal arteries of Wistar-Kyoto spontaneously hypertensive rats have shown that wall thickening of the vasculature occurs prior to hypertension development and is present even under conditions where the blood pressure has been normalized throughout the animal's life. These latter observations suggest that some structural alterations in the blood vessels observed in hypertension are pressure independent and could be of etiological importance in the initiation of hypertension.

Altered muscle metabolism associated with vasoconstriction in spontaneously hypertensive rats

1998 ◽  
Vol 275 (6) ◽  
pp. E1007-E1015 ◽  
Author(s):  
Ji-Ming Ye ◽  
Eric Q. Colquhoun
Keyword(s):  
Glucose Uptake ◽  
Spontaneously Hypertensive Rats ◽  
Perfusion Pressure ◽  
Lactate Production ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Response Curves ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

In the rat muscle vascular bed, vasoconstrictors either increase or decrease oxygen consumption (V˙o 2). The present study compared the effects of norepinephrine (NE), angiotensin II (ANG II), and 5-hydroxytryptamine (5-HT) on vasoconstriction-associated metabolism in the constant-flow perfused hindlimb of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) in the absence of insulin. Basal perfusion pressure,V˙o 2, glucose uptake, and lactate production were increased by 21.4, 11.9, 46.4, and 44.9% ( P < 0.05 for all), respectively, in SHR, which also had higher blood pressure and metabolic rate ( P < 0.05) in vivo. Dose-response curves for NE-induced perfusion pressure,V˙o 2, and lactate production in SHR were shifted to the left compared with WKY. Associated with the increased perfusion pressure, NE-inducedV˙o 2 and glucose uptake were both decreased ( P < 0.01), particularly at high concentrations. These differences were unaffected by 10 μM propranolol but were all diminished by further addition of prazosin (2.5 nM). ANG II stimulatedV˙o 2, glucose uptake, and lactate production in both strains, but the increased lactate production was smaller in SHR ( P < 0.05) with a proportional decrease ( P< 0.05) in glucose uptake. Conversely, 5-HT decreasedV˙o 2 in both strains ( P < 0.01), and this effect was greater in SHR ( P < 0.01). These data suggest that SHR muscle thermogenesis and glucose uptake are impaired during vasoconstriction, especially in response to NE.

Abstract 13102: Brain Angiotensin II Type1 Receptor Blockade Ameliorates the Development of Atrial Fibrillation via Sympathoinhibition Independent of Depressor Response in Hypertensive Rats

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tomomi Nagayama ◽  
Yoshitaka Hirooka ◽  
Takuya Kishi ◽  
Yasushi Mukai ◽  
Shujiro Inoue ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renin Angiotensin System ◽  
Atrial Fibrosis ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Depressor Response ◽  
Intracerebroventricular Infusion ◽  
Echocardiographic Parameters ◽  
Wistar Kyoto

Background: Previous studies demonstrated that the pathophysiology of atrial fibrillation (AF) with hypertension is associated with sympathoexcitation or the renin-angiotensin system. Conventional therapies, however, do not sufficiently prevent the development of AF. We reported that sympathoexcitation via brain angiotensin type1 receptors (AT1R) plays an important role in hypertension. Here we examined the hypothesis that brain AT1R-induced sympathoexcitation contributes to the development of AF in hypertension. Methods and Results: Sixteen-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY) were divided into 4 groups and administered treatment for 2 weeks, as follows: 1) SHRSP treated with intracerebroventricular infusion (ICV) of vehicle, S-VEH; 2) SHRSP treated with ICV of the AT1R blocker, losartan (1 mg/kg/day), S-LOS; 3) SHRSP treated with oral administration of hydralazine (100 mg/L in drinking water), S-HYD; 4) WKY treated with ICV of vehicle, W-VEH. Systolic blood pressure was significantly lower in both S-LOS and S-HYD than in S-VEH (201.0±1.7 and 172.4±4.0 vs. 233.0±3.5 mmHg, n=7-8/group, respectively, P<0.05). Urinary norepinephrine excretion for 24 hours as an indicator of sympathoexcitation was significantly reduced in S-LOS, but increased in S-HYD despite the larger depressor response. The induction rates of AF by transesophageal burst pacing were higher in S-VEH and S-HYD than in S-LOS and W-VEH (96±2% and 92±4% vs. 74±6% and 71±9%, n=7-8/group, respectively, p<0.05). AF duration was markedly inhibited in S-LOS, but not in S-HYD (Figure). Interstitial atrial fibrosis and echocardiographic parameters did not differ among SHRSP groups. Conclusions: Blockade of brain AT1R lowered the inducibility and sustainability of AF via sympathoinhibition independent of depressor response in hypertensive rats. We conclude that brain AT1R is a potential target of treatment for AF with hypertension.

Calcium reactivity and antagonism in portal veins from spontaneously hypertensive and normotensive rats

1984 ◽  
Vol 62 (1) ◽  
pp. 146-150 ◽  
Author(s):  
A. L. Harris ◽  
V. C. Swamy ◽  
D. J. Triggle
Keyword(s):  
Inhibitory Activity ◽  
Spontaneously Hypertensive Rats ◽  
Age Groups ◽  
Induced Responses ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Activity Frequency ◽  
Blood Pressures ◽  
Portal Veins ◽  
Wistar Kyoto

Reactivities of portal veins from spontaneously hypertensive rats (SHR) and normotensive controls (Wistar Kyoto, WKY) at 5–7 and 15–17 weeks of age were compared. Systolic blood pressures were not different at 5–7 weeks but those of SHR were significantly elevated (177 ± 4 mmHg) (1 mmHg = 133.322 Pa) at 15–17 weeks. Spontaneous activity, frequency, and tension were greater in SHR for both age groups. Young SHR were more sensitive to K+ at 5–7 weeks but less sensitive at 15–17 weeks than age-matched WKY rats. Sensitivity to Ca2+ in a K+-depolarizing medium was higher in SHR than in WKY for both age groups. Maximum tension responses to K+ or Ca2+ were greater in SHR. The Ca2+ channel antagonists nifedipine, nitrendipine, and nisoldipine were potent inhibitors of both noradrenaline- and K+-induced responses but did not show differences in inhibitory activity between WKY and SHR.

Estrogen attenuation of the development of hypertension in spontaneously hypertensive rats

1977 ◽  
Vol 233 (3) ◽  
pp. H369-H373 ◽  
Author(s):  
J. M. Hoeg ◽  
L. R. Willis ◽  
M. H. Weinberger
Keyword(s):  
Blood Pressure ◽  
Corn Oil ◽  
Normal Growth ◽  
Estrogen Treatment ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Lower Blood ◽  
Blood Pressures ◽  
Wistar Kyoto ◽  
Estrogen Administration

To examine the effects of estrogen on the development of high blood pressure in rats with a genetic predisposition toward hypertension, we administered to rats of the spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) strains 0.05 mg mestranol daily from ages 4 to 13 wks. Control animals of each strain received corn oil placebos. Systolic blood pressure was measured by a microphonic tail-cuff technique twice a week after the rats were 6 wks of age. Estrogen treatment in SHR was associated with a significant reduction in the level of hypertension attained, but estrogen treatment had no effect on blood pressure in WKY. Estrogen prevented normal growth in SHR and WKY, but this effect (reproduced in another group of SHR and WKY by restriction of food intake) was not related to the lower blood pressures seen in estrogen-treated SHR. Thus, it appeared that estrogen administration attenuated the rise in blood pressure normally seen in SHR and that this attenuation was independent of the estrogenic effect on body weight.

Cell Membrane Microviscosity and Ca2+-Mg2+-ATPase Activity do Not Contribute to Hypertension in the Spontaneously Hypertensive Rat Model

1993 ◽  
Vol 85 (5) ◽  
pp. 585-591 ◽  
Author(s):  
Robert I Norman ◽  
Navtej Achall
Keyword(s):  
Blood Pressure ◽  
Atpase Activity ◽  
Spontaneously Hypertensive Rats ◽  
Spontaneously Hypertensive Rat ◽  
Hypertensive Rats ◽  
Membrane Microviscosity ◽  
Spontaneously Hypertensive ◽  
Blood Pressures ◽  
Wistar Kyoto ◽  
Spontaneously Hypertensive Rat Model

1. The relationships between systolic blood pressure and altered erythrocyte Ca2+-Mg2+-ATPase activity and membrane microviscosity were assessed in membranes prepared from 20-week-old female Wistar-Kyoto normotensive and spontaneously hypertensive rats obtained from two different sources (Charles River and Harlan OLAC) and a second filial (F2) generation derived from a cross between Wistar-Kyoto rats and spontaneously hypertensive rats from one source (Charles River). 2. Spontaneously hypertensive rats from both sources had systolic blood pressures significantly higher than those of Wistar-Kyoto animals (P <0.05; 151 + 4 and 110 + 3 mmHg, Charles River; 155 + 4 and 122 + 4 mmHg, Harlan OLAC). The systolic blood pressures for the F2 rat population ranged between 73 and 168 mmHg. 3. Ca2+-Mg2+-ATPase activity was measured as ATP-dependent 45Ca2+ uptake into inside-out vesicles and microviscosity assessed by the measurement of polarization anisotropy of membrane incorporated fluorescent probes including 1,6-diphenyl-1,3,5-hexatriene, trimethylamino-1,6-diphenyl-1,3,5-hexatriene and a series of anthroyloxy fatty acids. 4. Contrary to previous studies, no relationship between adult systolic blood pressure and erythrocyte Ca2+-Mg2+-ATPase activity or general or localized membrane microviscosity was indicated by the comparison of spontaneously hypertensive and Wistar-Kyoto animals or in the analysis of the F2 rat population. 5. These results suggest that Ca2+-Mg2+-ATPase activity and membrane microviscosity are causally unrelated to hypertension in these animals. On the assumption that biophysical properties of the erythrocyte membrane reflect those of smooth muscle, our results suggest that membrane alteration does not play a significant role in the pathogenesis of hypertension in the spontaneously hypertensive rat model.

Sign in / Sign up

Export Citation Format

Share Document