Activation of peripheral respiratory chemoreceptors provokes respiratory and cardiovascular reflexes, providing a novel understanding of pathogenic mechanism of hypertension. Here we hypothesize that activation of peripheral respiratory chemoreceptors by hypoxia causes enhanced cardiorespiratory activity in conscious spontaneously hypertensive rats (SHRs). Using whole body plethysmography in combination with radio telemetry, pulmonary ventilation, arterial blood pressure and heart rate were examined in SHRs and Wistar-Kyoto (WKY) rats. We found that exposure to hypoxia induced greater increases in tidal volume and minute ventilation volume in SHRs compared to WKY rats. In addition, hypoxia caused a robust increase in arterial blood pressure and heart rate in SHRs relative to WKY counterparts. After carotid body denervation, the hypoxic ventilatory response was significantly decreased in both SHRs and WKY rats, but without significant difference between the two strains; moreover, the differences of arterial blood pressure and heart rate changes during hypoxic exposure were statistically insignificant between SHRs and WKY rats. It is concluded that hypoxia remarkably potentiates cardiorespiratory activity in the SHRs, suggesting an enhanced sensitivity of carotid bodies to hypoxia.
Animals ; Blood Pressure ; Heart Rate ; Hypertension ; physiopathology ; Hypoxia ; physiopathology ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY

Objective: To study the effects of aerobic exercise training on renal fibrosis in spontaneously hypertensive rats (SHR), and to explore the protective effect of exercise on renal damage in hypertensive rats. Methods: Eight-week-old male SHR and Wistar Kyoto rats of the same age (WKY) were randomly divided into 4 groups (n=6): sedentary WKY control group (WKY-S), sedentary SHR control group (SHR-S), low-intensity exercise group (SHR-L) and medium-intensity exercise group (SHR-M). SHR-L group and SHR-M group were set at a slope of 0° at 14 m/min (35% of the maximum aerobic speed) and 20 m/min (50% of the maximum aerobic speed), running on a sports treadmill for 14 weeks, 5 times a week, and 60 min each time. WKY-S and SHR-S groups were kept quietly. Blood pressure was measured 72 hours after exercise training. And the serum levels of creatinine (Scr) and BUN were detected. The morphology of renal tissue was observed by hematoxylin and eosin (HE) staining. The collagen deposition of renal tissue was observed by Masson staining, and the renal collagen volume fraction (CVF) was calculated. Results: Compared with WKY-S group, blood pressure, serum Scr and BUN, kidney CVF levels and AngⅡ, AT1R, TGF-β, α-SMA, CTGF expressions in SHR-S group were increased significantly (P＜0.05). Compared with SHR-S group, blood pressure, serum Scr and BUN, kidney CVF level and AngⅡ, AT1R, TGF-β, α-SMA, CTGF expressions in SHR-L and SHR-M groups were decreased significantly (P＜0.05) and the decreasing trend was more obvious in SHR-M group (P＜0.05). Conclusion: Aerobic exercise can improve renal fibrosis and renal function in spontaneously hypertensive rats by inhibiting the AngⅡ-AT1R-TGF-β pathway.
Animals ; Fibrosis ; Kidney Diseases ; Male ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Transforming Growth Factor beta

The hyperactivity of cholinergic system in the RVLM of spontaneously hypertensive rats (SHR) may contribute to the sustained elevation of blood pressure. However, the hyperactivity mechanisms of cholinergic system are controversial. Thus, to clarify the mechanisms of cholinergic hyperactivity in RVLM of the SHR, we studied the activities of enzymes that participate in the biosynthesis and degradation of acetylcholine (ACh) and the density of muscarinic receptors in RVLM of the 14- to 18-week-old SHR and age-marched Wistar Kyoto rats (WKY). Choline acetyltransferase activity was far greater in RVLM of SHR than that of WKY. (3H)ACh release from RVLM was also greater in SHR than in WKY. Acetylcholinesterase activity and (3H)NMS binding of RVLM slice of SHR were not significantly different from that of WKY. These results suggest that the enhanced cholinergic mechanisms in the RVLM of SHR is due to the enhanced presynaptic cholinergic tone rather than the altered postsynaptic mechanisms.
Acetylcholine ; Acetylcholinesterase ; Blood Pressure ; Choline O-Acetyltransferase ; Rats, Inbred SHR* ; Rats, Inbred WKY ; Receptors, Muscarinic

OBJECTIVETo investigate the association between insulin and hypertension.

METHODSTwenty spontaneously hypertension rats(SHR) and twenty Wistar-Kyoto rats(WKY) were randomly divided into two groups control group and insulin injection group. Systolic blood pressure(SBP),pulse rate(P), fasting blood sugar(FBS), fasting serum insulin(FINS) and insulin sensitivity index(ISI) were observed or calculated before and at the 60th day of the experiment.

RESULTS(SBP 165.5+/-5.8 compared with 108.2+/-4.7mmHg,P<0.01), P(405.8+/-19.6 compared with 336.6+/-9.6 /min P<0.01), FINS (6.89+/-0.99 compared with 5.78+/-0.91mU/L,P<0.05)of SHR were higher than those of WKY before experiment, but there was a lower ISI of SHR -3.397+/-0.191 compared with -3.085+/-0.132,P<0.01 . There were increases of SBP(210.0+/-8.5 compared with 184.3+/-8.0 mmHg,P<0.01),P(452.2+/-13.9 compared with 406.0+/-22.7/min P<0.01) and FINS (28.37+/-3.86 compared with 7.32+/-0.87 mU/L,P<0.01) in insulin injection group of SHR than those in controls,but ISI -4.119+/-0.260 compared with -3.604+/-0.174 P<0.01 decreased in insulin injection group; The same changes were observed in WKY rats after insulin injection (131.6+/-6.7 compared with 110.4+/-5.1 mmHg, 378.2+/-13.2 compared with 347.1+/-14.9/min 22.64+/-2.13 compared with 5.55+/-0.77 mU/L,-3.474+/-0.214 compared with 3.094+/-0.191 P<0.01 respectively).

CONCLUSIONInsulin resistance and hyperinsulinemia exist in SHR,chronic hyperinsulinemia may increase SBP and P,decrease ISI of WKY and SHR.

Animals ; Blood Glucose ; analysis ; Hyperinsulinism ; etiology ; Hypertension ; blood ; physiopathology ; Insulin Resistance ; Male ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Systole

MicroRNAs (miRNAs) are genomically encoded non-protein-encoding small RNAs, which negatively regulate target gene expression at post-transcriptional level. The present study aimed to investigate whether disorders of miRNAs system were involved in the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). MiRanda, Target Scan and PicTar were utilized for predictive analysis of miRNAs and target genes. MiR-1, miR-133a, miR-155 and miR-208 were selected as the candidate miRNAs potentially related to blood pressure. The expression levels of miR-1, miR-133a, miR-155 and miR-208 in the aorta of 4-, 8-, 16- and 24-week-old SHR and age-matched Wistar-Kyoto (WKY) rats were detected by real-time RT-PCR. The mRNA levels of angiotensin II receptor type 1 (AGTR1a), angiotensin II receptor associated protein (AGTRAP), divalent metal transporter 1 (DMT1), low-density lipoprotein-related protein 1B (LRP1B), fibroblast growth factor-7 (FGF-7), protocadherin 9 precursor (PCDH9), chloride channel protein 5 (CLCN-5), small conductance calcium activated potassium channel protein 3 (KCNN3) and thyroid hormone receptor associated protein 1 (THRAP1), which were predicted to be target genes of differentially expressed miRNAs, were further detected by real-time RT-PCR. The results obtained showed that the expression levels of miR-1, miR-155 and miR-208 in the aorta were significantly different from those in the heart of WKY rats. The miR-155 level was significantly lower in aorta of 16-week-old SHR than that of age-matched WKY rats (P<0.05), but there was no difference between SHR and WKY rats in other age groups. In addition, miR-155 level was negatively correlated to blood pressure (r=-0.525, P<0.05). Both in WKY rats and SHR, miR-208 was most abundantly expressed in 4-week-old rats, but declined significantly in 8-, 16- and 24-week-old rats (P<0.05). No difference in miR-208 levels was observed between age-matched SHR and WKY rats. Moreover, miR-208 expression in aorta was negatively correlated with blood pressure (r=-0.400, P<0.05) and age (r=-0.684, P<0.0001). Neither miR-1 nor miR-133a was differentially expressed in SHR and WKY rats in different age groups. The mRNA levels of predicted target genes were not correlated to miR-155 or miR-208 levels. These results indicate that miR-155 is less expressed in the aorta of adult SHR compared with that of WKY rats and is negatively correlated with blood pressure, suggesting it is possibly involved in the development and pathologic progress of hypertension. The miR-208 expression in rat aorta declines with aging and it may play a role in the blood vessel development.
Animals ; Aorta ; metabolism ; Blood Pressure ; Hypertension ; metabolism ; MicroRNAs ; metabolism ; RNA, Messenger ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY

OBJECTIVETo investigate the role of hypertension in the pathogenesis of cerebral aneurysms in rats.

METHODSTwenty spontaneous hypertensive rats (SHR) and 10 Wistar-Kyoto rats (WKY) were included in this observational study. Animals were fed with normal diet and drinking water. No experimental modifications were undertaken in either group. They were sacrificed at one year of age, the bifurcations of the circle of Willis were dissected and longitudinal serial sections were prepared for light microscopic and transmission electron microscopic study.

RESULTSIn the SHR group, 2 of the 20 rats formed an aneurysm respectively at the bifurcations of the basilar artery. As revealed by electron microscopy, injury at the bifurcation of the artery first occurred on the steeper side of the intimal pad. Furthermore, loss of endothelial cells, small depressions on the intima, disruptive internal elastic lamina and lymphocytes or red blood cells infiltration were noted at the steeper side of the intimal pad. No significant changes were observed in WKY group.

CONCLUSIONSCerebral aneurysms can form spontaneously in SHR without ligation of the common carotid artery and without a diet containing beta-aminoproprionitrile. Long-standing systemic arterial hypertension is one of the etiological factors that contributes to aneurysm formation in SHR rats.

Animals ; Cerebral Arteries ; pathology ; Hypertension ; complications ; Intracranial Aneurysm ; etiology ; pathology ; Male ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY

OBJECTIVETo investigate the changes of the expressions of the nerve growth factor (NGF) and its mRNA in the prostate tissues of spontaneously hypertensive rats (SHR) of different ages and their significance.

METHODSSHRs and normotensive Wistar Kyoto (WKY) rats were killed at 1 month (young), 6 months (adult) and 12 months (aging), respectively, 5 in each group. Their prostate indexes were calculated, and the expressions of NGF and its mRNA in the ventral prostate tissue were detected by immunohistochemistry and RT-PCR.

RESULTSThe prostate indexes of the SHR and WKY groups were 1.16 +/- 0.06 and 1.03 +/- 0.09 at 1 month, 1.12 +/- 0.14 and 0.93 +/- 0.07 at 6 months, and 1.11 +/- 0.05 and 0.96 +/- 0.09 at 12 months, significantly higher in the former group than in the latter either at 6 or at 12 months (P < 0.05), but with no obvious difference at 1 month (P > 0.05). The expressions of NGF and its mRNA in the ventral prostate tissue were detected in all groups, and elevated gradually with the increase of age (P < 0.05). Among those of the same age, the expression levels were markedly higher in the SHR than in the WKY group (P < 0.05).

CONCLUSIONIn SHRs with benign prostate hyperplasia (BPH), the enhanced excitation of the sympathetic nervous system may be a common mechanism underlying BPH and hypertension, and NGF plays an important role in it.

Aging ; Animals ; Male ; Nerve Growth Factors ; metabolism ; Prostate ; metabolism ; pathology ; Prostatic Hyperplasia ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY

Angiotensin II ; metabolism ; Animals ; Cardiomyopathy, Hypertrophic ; etiology ; metabolism ; Hypertension, Renal ; complications ; Male ; Myocardium ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Rats, Wistar

The aim of the present study was to investigate the effects of ketamine, imipramine, and ketamine plus imipramine on chronic depression-like behaviors of Wistar Kyoto (WKY) rats and underlying mechanism. Six-week-old Wistar rats were used as normal control. WKY rats, depression model animal, were injected intraperitoneally with ketamine (1 week, replaced with saline in 2(nd) week), imipramine (2 weeks), or ketamine in combination with imipramine. The depression-like behaviors were assessed by sucrose preference and forced swimming tests. Protein expressions of β form of calcium/calmodulin-dependent protein kinase type II (βCaMKII) and membrane fraction of glutamate receptor 1 (GluR1) were measured in corresponding brain tissue with Western blot. The results showed that, compared with Wistar rats, WKY rats exhibited decreased sucrose preference and extended immobility time. Ketamine alone did not affect depression-like behaviors of WKY, whereas imipramine or its combination with ketamine could significantly decrease the immobility time. Compared with Wistar rats, WKY rats showed up-regulated levels of βCaMKII and membrane GluR1 protein expressions in habenula, and down-regulated level of membrane GluR1 protein expressions in the prefrontal cortex. Imipramine or its combination with ketamine could reverse these changes of protein expressions in WKY rats. There was no difference in reversing effect between imipramine and its combination with ketamine. Ketamine alone did not affect the βCaMKII and membrane GluR1 protein expressions in the habenula, but increased membrane GluR1 protein expression in the prefrontal cortex of WKY rats. These results suggest 2-week imipramine treatment significantly improves depressive behavior in WKY rats; however, the addition of ketamine in the first week fails to enhance the effect of imipramine. The underlying mechanisms of imipramine's anti-depressive effect may be associated with the down-regulation of βCaMKII and membrane GluR1 in the habenula, as well as the up-regulation of membrane GluR1 in the prefrontal cortex.
Animals ; Brain ; Depression ; Depressive Disorder ; Disease Models, Animal ; Down-Regulation ; Imipramine ; Ketamine ; Male ; Rats ; Rats, Inbred WKY ; Swimming ; Up-Regulation

OBJECTIVETo investigate the effects of spironolactone on the concentration of collagen type I, III in the myocardium of spontaneous hypertension rats (SHR).

METHODSTwenty 8-week male SHR were assigned randomly into spironolactone (SHR-SPIRO, n=10) and control groups (SHR-CON, n=10), sex-age matched Wistar Kyoto rats (WKY group, n=7) were also served as controls. The rats of SHR-SPIRO group were given 20 mg/(kg*d) of spironolactone, the rats of SHR-CON and WKY groups were given the same volume of distilled water. After 16 weeks, the concentration of collagen type I was analyzed with Western blot. The areas of collagen type I and III were observed under polarized light microscopy and the ratio of type I/III collagen was calculated through accumulation score.

RESULTSCompared with WKY group,the concentration of collagen type I in SHR-CON group was significantly higher (1.87 ±0.2 Compared with 1.21 ±0.7, P<0.05). After 16 weeks of treatment the concentration of collagen type I (1.42 ±0.05 Compared with 1.87 ±0.2, P<0.05) and I/III ratio in SHR-SPIRO group were significantly reduced (15.64 ±1.34 Compared with 20.8 ±3.04, P<0.05) compared with SHR-CON group; but there were no differences in accumulation area scores of collagen type III among three groups (368.3 ±30.2 Compared with 481.6 ±32.4 Compared with 406.2 ±45.3, P>0.05).

CONCLUSIONThe deposition of collagen type I in myocardium may be involved in myocardial fibrosis of SHR, and spironolactone can decrease the concentration of collagen type I, which may be one of the mechanisms for its therapeutic effects.

Animals ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Male ; Mineralocorticoid Receptor Antagonists ; pharmacology ; Myocardium ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Spironolactone ; pharmacology