Differential participation of calcium-activated potassium channel in endothelium-dependent hyperpolarization-type relaxation in superior mesenteric arteries of spontaneously hypertensive rats

2018 ◽  
Vol 96 (8) ◽  
pp. 839-844
Author(s):  
Makoto Ando ◽  
Takayuki Matsumoto ◽  
Shota Kobayashi ◽  
Maika Iguchi ◽  
Kumiko Taguchi ◽  
...  

The purpose of this study was to determine the relationship of KCa channels to endothelium-dependent hyperpolarizing factor (EDHF)-mediated relaxation induced by acetylcholine (ACh) in the superior mesenteric arteries of 7-month-old spontaneously hypertensive rats (SHR). Upon inhibition of nitric oxide synthase and cyclooxygenase, ACh-induced EDHF-mediated relaxation was found to be weaker in SHR than in age-matched Wistar Kyoto rats (WKY). These relaxations in both group were attenuated by combined treatment with small-conductance and intermediate-conductance Ca2+-activated K+ channels (SKCa and IKCa) inhibitors, with the exception of relaxation resistant to inhibition of these channels in SHR (vs. WKY). Treatment with large-conductance Ca2+-activated K+ channels (BKCa) inhibitor specifically attenuated relaxation in SHR, but not in WKY. Protein expression of IKCa and SKCa in the arteries did not differ between the 2 groups, whereas ratio of sloβ1 subunit to α subunit of BKCa was increased in SHR (vs. WKY). These results suggest that EDHF-mediated relaxations in superior mesenteric arteries are impaired in SHR, and utilize components of BKCa in addition to SKCa/IKCa channel activities, that the increased participation of BKCa may be attributable to alterations in α and sloβ1 subunit ratio, and that components unrelated to KCa activity may also contribute to the difference between SHR and WKY arteries.

BMC Urology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuki Kyoda ◽  
Koji Ichihara ◽  
Kohei Hashimoto ◽  
Ko Kobayashi ◽  
Fumimasa Fukuta ◽  
...  

Abstract Background Neuroendocrine (NE) cells may have an impact on the development and initial growth of benign prostatic hyperplasia (BPH) according to previous human studies. Methods To explore the relationship of NE cells and BPH development, we compared the density of NE cells and also prostatic weight in spontaneously hypertensive rats (SHR), which develop by aging, and Wistar-Kyoto rats (WKY) as control. The total weights of the epithelium and stroma in the ventral lobes of 8-, 12, 16-, 28- and 56-week-old SHR and WKY were calculated using Image J software. NE cells in the ventral prostatic ducts (VPd) were quantified using immunohistochemical staining for serotonin. Results Although there was no significant difference in the estimated total weight of the epithelium and stroma in the ventral lobes adjusted by body weight (ES weight) between the two groups at 8, 12 and 16 weeks of age, ES weight was significantly greater in the SHR group than in the WKT group at 28 and 56 weeks. The density of NE cells in the VPd decreased with aging in the WKY group, whereas it was sustained until 16 weeks and then decreased with aging in the SHR group. The difference in the density between the two groups was most marked at 16 weeks of age. Conclusion In the natural history of BPH, NE cells may play an important role in the initial development of BPH because sustained density of NE cells in the VPd precedes the development of prostatic hyperplasia.


1996 ◽  
Vol 270 (1) ◽  
pp. H1-H6 ◽  
Author(s):  
A. S. Izzard ◽  
S. J. Bund ◽  
A. M. Heagerty

To investigate myogenic tone during the developmental and established phases of hypertension, segments of distal (6th order) mesenteric arteries from spontaneously hypertensive rats (SHR) at 5 and 20 wk were isolated and pressurized in vitro and compared with vessels from age-matched Wistar-Kyoto (WKY) control animals. At 5 wk, tone was significantly enhanced in the SHR. At 20 wk tone was no longer significantly increased over a wide pressure range, although arteries from the SHR were able to maintain diameter at all pressures studied, whereas vessels from the WKY exhibited forced distension at 180 and 200 mmHg. From the relative slope of the pressure-diameter relationship (myogenic index), no increase in peak myogenic responsiveness was observed in arteries from the SHR at either time point. Passive lumen diameters were significantly decreased in arteries from SHR at both time points. From the total and passive midwall circumference-tension relationships, total tension was observed at a reduced midwall circumference in the SHR, but increased absolute levels of total tension were not observed. The normalized midwall circumference-tension relationships in the two strains revealed increased total tension due to active tension development at a reduced normalized circumference at 5 wk in the SHR. At 20 wk the normalized midwall circumference-tension relationships in the two strains were identical. These results demonstrate that myogenic tone in mesenteric arteries is enhanced during the development of hypertension but not when it is established, except at high intraluminal pressures.


1981 ◽  
Vol 240 (6) ◽  
pp. H927-H933
Author(s):  
L. J. Heller

Isovolumetric pressure-producing properties of isolated Langendorf-perfused hypertrophied ventricles from adult spontaneously hypertensive rats (SHR) were compared with those of nonhypertrophied ventricles from adult Wistar-Kyoto rats (WKY). SHR ventricles were found to produce greater systolic pressure than WKY ventricles when subjected to similar stimulation and perfusion conditions. Correction for the differences in ventricular mass eliminated the difference between groups. Apparent diastolic pressure at high stimulus rates was higher in SHR than WKY, and SHR developed exaggerated aftercontractions following cessation of high-frequency stimulation. Refractory periods of hypertrophied ventricles determined by paired-pulse stimulation were not found to be different from nonhypertrophied ventricles, but hyperexcitable periods of SHR ventricles were significantly longer than WKY ventricles. In addition, the intrinsic ventricular rate of SHR preparations was significantly greater than that of WKY.


1987 ◽  
Vol 65 (2) ◽  
pp. 230-235 ◽  
Author(s):  
C. Subah Packer ◽  
Newman L. Stephens

Prolonged isometric relaxation in hypertensive aortic and caudal arterial smooth muscle has been demonstrated; however, isobaric relaxation in resistance arteries is more pertinent to studies in hypertension. A comparative study of mesenteric arterial isobaric relaxation times was made using spontaneously hypertensive rats (SHR), normotensive Wistar–Kyoto rats (WKY), and MK-421 treated SHR (treatment commenced at 8 weeks of age and was maintained until sacrifice). Relaxation rates of vessels constricting against a range of pressures and achieving different degrees of narrowing or changes in circumference were analyzed. Comparisons were made between SHR, WKY, and MK-421 treated SHR arteries that had constricted from the same initial circumference and against the same magnitude of pressure. The SHR mesenteric arteries relaxed at a slower rate than did the WKY vessels. The normotensive MK-421 treated SHR showed the same prolonged relaxation rate as did the untreated SHR preparations. Thus the slower rate of relaxation in SHR arteries does not appear to be a consequence of the hypertension. Such prolonged time for narrowing would function to increase the average peripheral resistance and thus may contribute to the initiation and maintenance of increased blood pressure.


2012 ◽  
pp. S145-S153 ◽  
Author(s):  
Z. CHARVÁTOVÁ ◽  
I. OŠŤÁDALOVÁ ◽  
J. ZICHA ◽  
J. KUNEŠ ◽  
H. MAXOVÁ ◽  
...  

Hypertension is the risk factor of serious cardiovascular diseases, such as ischemic heart disease and atherosclerosis. The aim of the present study was to analyze the development of cardiac tolerance to ischemia in neonatal spontaneously hypertensive rats (SHR) and possible protective effect of ischemic preconditioning (IP) or adaptation to intermittent high-altitude hypoxia (IHAH). For this purpose we used 1- and 10-day-old pups of SHR and their normotensive control Wistar Kyoto rats (WKY). Isolated hearts were perfused in the Langendorff mode with Krebs-Henseleit solution at constant pressure, temperature and rate. Cardiac tolerance to ischemia was expressed as a percentage of baseline values of developed force (DF) after global ischemia. IP was induced by three 3-min periods of global ischemia, each separated by 5-min periods of reperfusion. IHAH was simulated in barochamber (8 h/day, 5000 m) from postnatal day 1 to 10. Cardiac tolerance to ischemia in 1-day-old SHR was higher than in WKY. In both strains tolerance decreased after birth, and the difference disappeared. The high cardiac resistance in 1- and 10-day-old SHR and WKY could not be further increased by both IP and adaptation to IHAH. It may be concluded that hearts from newborn SHR are more tolerant to ischemia/reperfusion injury as compared to age-matched WKY; cardiac resistance decreased in both strains during the first ten days, similarly as in Wistar rats.


2008 ◽  
Vol 86 (11) ◽  
pp. 737-744 ◽  
Author(s):  
Yu-Jing Gao ◽  
Lu-Fang Yang ◽  
Shelley Stead ◽  
Robert M.K.W. Lee

The effect of an increased blood flow on vascular remodeling was studied in the mesenteric arteries of 11–12-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar–Kyoto rats (WKY). Increased blood flow was induced by selective ligation of mesenteric arteries. Nearby arteries with normal blood flow were used as controls. 7–10 days after the ligation procedure, mesenteric arteries were fixed in situ at maximal relaxation by perfusion fixation. Morphometric measurement of vascular dimension was carried out with confocal microscopy. Apoptotic cells were detected by the TdT-mediated dUTP nick-end labelling method. Cell growth was quantified by using proliferating cell nuclear antigen (PCNA) in sections of paraffin-embedded vessels. In SHR, elevated blood flow increased the vessel wall dimension and the number of smooth muscle cell (SMC) layers and also increased the wall-to-lumen ratio and the number of PCNA-positive SMC, but did not change lumen size or number of apoptotic SMC. In WKY, on the other hand, increased blood flow resulted in an increase in lumen diameter, a reduction of apoptotic SMC, but no change in wall-to-lumen ratio, number of SMC layers, or number of PCNA-positive SMC. These results showed that mesenteric arteries from hypertensive and normotensive rats respond to an increase in blood flow differently: a lumen enlargement with reduced SMC apoptosis in WKY, but an increased wall-to-lumen ratio with enhanced SMC growth in SHR. Although it remains to be determined whether flow alteration is one of the initiating factors in the development of vascular remodeling in hypertension, we speculate that an increase in cardiac output, and therefore an increase in shear stress that occurs in young SHR, contributes to vascular remodelling in this model of hypertension.


1990 ◽  
Vol 258 (1) ◽  
pp. F175-F182 ◽  
Author(s):  
W. R. Jacobs ◽  
C. M. Ferrari ◽  
P. C. Brazy ◽  
L. J. Mandel

Cytosolic free calcium (Caf) was measured in isolated renal cortical tubules from spontaneously hypertensive rats (SHR) and age-matched control Wistar-Kyoto (WKY) rats to evaluate whether the onset of hypertension is associated with a change in Caf. At the same time, the cellular mechanism by which differences in Caf occur between these two strains of rats was examined. Caf was significantly lower in renal tubules from 4- to 5-wk (142 +/- 6 vs. 187 +/- 15 nM), 6- to 7-wk (138 +/- 15 vs. 187 +/- 8 nM), and 8- to 9-wk-old (161 +/- 5 vs. 216 +/- 9 nM) SHR compared with age-matched WKY. The lower Caf in SHR tubules was considered to be the result of either an increase in Ca efflux or a reduction in Ca permeability. To the extent that metabolic inhibitors increased Caf but did not alter the difference between SHR and WKY, a primary difference in Caf efflux was excluded. Conversely, when Ca permeability was altered, either with Ca ionophores or incubation in Ca-free medium, Caf changed in the appropriate direction and the difference between SHR and WKY was no longer apparent. These results demonstrate that 1) the previously reported increase in Caf in circulating cells is not a universal feature of hypertension and 2) the lower Caf in renal tubules from SHR appears to be related to a lower Ca permeability. Whether the differences in Caf between SHR and WKY is a permissive factor for the renal contribution to hypertension remains to be elucidated.


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