The Effects of Renal Nerve Denervation on Blood Pressure and Target Organs in Different Hypertensive Rat Models

Background. Hypertension contributes to the progression of cardiac remodeling and renal damage. In turn, renal sympathetic hyperactivation showed elevated sympathetic nervous system activity and led to blood pressure increase in certain patients. The purpose of this study was to observe the effect of renal nerve denervation on blood pressure and target organ changes in two hypertensive rat models. Methods. Hypertensive rats were randomly divided into a renal denervation (RDN) group and sham operation group. Wistar–Kyoto (WKY) rats of the same age were set as the baseline control group. In the secondary hypertension model, SD rats were randomly divided into five groups. Blood pressure and bodyweight were measured every week until they were euthanized. Results. The two rat models underwent RDN at key timepoints. At these timepoints, the hearts and kidneys were collected for norepinephrine and angiotensin II measurements and histological analysis. Conclusion. RDN performed before development of hypertension showed a significant antihypertensive effect on the secondary hypertension model.

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P4562Bilateral sphenopalatine ganglion block reduces blood pressure in never treated hypertensive patients. A randomized controlled study

European Heart Journal ◽

10.1093/eurheartj/ehz745.0953 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

H Triantafyllidi ◽

C Arvaniti ◽

A Schoinas ◽

D Benas ◽

D Voutsinos ◽

...

Keyword(s):

Blood Pressure ◽

Blood Pressure Monitoring ◽

Controlled Study ◽

Control Group ◽

Sham Operation ◽

Study Group ◽

Sphenopalatine Ganglion ◽

Night Time ◽

Hypertensive Patients ◽

Sham Operation Group

Abstract Background Sphenopalatine ganglion (SPG) area is connected through sympathetic fibers with the central nervous system. We aimed to study the effect of SPG block in blood pressure (BP) in never treated patients with stage I-II essential hypertension. Methods We performed bilateral SPG block with lidocaine 2% in 53 newly diagnosed and never treated hypertensive patients (study group, mean age 49+12 years, 38 men) and a sham operation with water for injection in 11 patients (control group, mean age 51+12 years, 8 men). All patients have been subjected to 24 hour ambulatory blood pressure monitoring prior and a month after the SBG block in order to estimate any differences in blood pressure parameters derived from ABPM (blood pressure, heart rate, blood pressure load and variability). We defined as responders to SBG block those patients with a 24h average SBP decrease >5 mmHg. Results In the study group, a month after SPG block: a. 24h average SBP and DBP were reduced by 1.3+7mmHg and 1.8+5 mmHg, respectively, and b. 24h average DBP (p=0.03), daytime DBP (p=0.01) and daytime DBP load (p=0.01) were significantly decreased. Interestingly, in the responders group (14/42, 33%) a month after SPG block: a. 24h average SBP and DBP were reduced by 9+4mmHg and 6.5+3 mmHg, respectively, b. SBP and DBP were decreased during overall 24h and daytime (p<0.001) and night-time periods (p=0.002 and p=0.02, respectively) and c. SBP load was decreased during daytime and night-time while DBP load was decreased during daytime (p<0.001). As it was expected, no differences regarding BP were found in the sham operation group. BP decrease after SPG block Conclusions We have proved that the minimally invasive option of the SPG block leads to blood pressure decrease, probably through SNS modulation. Moreover, due to its short-term anesthetic effect, SPG block might act as a method of selection of those hypertensives with an activated SNS before any other invasive procedure.

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Effect of renal denervation on prenatal programming of hypertension and renal tubular transporter abundance

AJP Renal Physiology ◽

10.1152/ajprenal.00123.2008 ◽

2008 ◽

Vol 295 (1) ◽

pp. F29-F34 ◽

Cited By ~ 59

Author(s):

Amit Dagan ◽

H. Moo Kwon ◽

Vangipuram Dwarakanath ◽

Michel Baum

Keyword(s):

Blood Pressure ◽

Renal Denervation ◽

Control Group ◽

Renal Nerves ◽

Sham Operation ◽

Protein Abundance ◽

Prenatal Programming ◽

Sham Operation Group ◽

Renal Tubular ◽

Type 3

Prenatal glucocorticoids are often administered to pregnant women to accelerate pulmonary maturation. We have demonstrated that administration of dexamethasone during specific periods of pregnancy in the rat causes hypertension in the offspring when they are studied as adults. The purpose of the present study was to determine whether the hypertension due to prenatal dexamethasone was mediated by renal nerves. We administered dexamethasone to rats daily for 4 days between days 15 and 18 of gestation. Rats underwent bilateral renal denervation or sham operation at 6 wk of age, and blood pressure was measured at 8 wk of age. Prenatal dexamethasone in the sham operation group resulted in an increase in blood pressure compared with vehicle-treated sham controls (134 ± 3 vs. 145 ± 3 mmHg, P < 0.05). Renal denervation did not affect blood pressure significantly in the prenatal vehicle-treated control group but resulted in normalization in blood pressure in the prenatal dexamethasone group and (130 ± 3 and 128 ± 5 mmHg, respectively). Prenatal dexamethasone increased type 3 Na+/H+ exchanger (NHE3), Na+-K+-2Cl− cotransporter (NKCC2), and Na+-Cl− cotransporter (NCC), but not α-, β-, and γ-epithelial Na+ channel (ENaC) protein abundance compared with controls. The increase in NHE3, NKCC2, and NCC protein abundance by prenatal dexamethasone was not seen in 8-wk-old rats 2 wk after renal denervation. Renal denervation did not affect NHE3, NKCC2, and NCC protein abundance in prenatal vehicle-treated animals. This study is consistent with renal nerves playing a role in mediating the hypertension by prenatal programming by dexamethasone.

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Hypoxic moderation of systemic hypertension in the spontaneously hypertensive rat

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1987.252.3.r554 ◽

1987 ◽

Vol 252 (3) ◽

pp. R554-R561 ◽

Cited By ~ 2

Author(s):

W. N. Henley ◽

A. Tucker

Keyword(s):

Blood Pressure ◽

Spontaneously Hypertensive Rat ◽

Metabolic Adaptation ◽

Systemic Hypertension ◽

Thyroid Status ◽

Blood Pressure Elevation ◽

Spontaneously Hypertensive ◽

Moderate Hypobaric Hypoxia ◽

Hypertensive Rat ◽

Wistar Kyoto

The mechanism by which chronic, moderate, hypobaric hypoxia attenuates systemic systolic blood pressure (SBP) in the spontaneously hypertensive rat (SHR) was investigated in a three-part study. In experiment 1, 10 wk of hypoxia (3,658 m altitude) commencing in 7-wk-old rats was partially effective in preventing the rise in SBP [hypoxic SHR (SHR-H) 154 mmHg vs. normoxic SHR (SHR-N) 180 mmHg; P less than 0.01]. When hypoxia was initiated in 5-wk-old SHR (experiments 2 and 3), protection against hypertension was nearly complete (experiment 2: SHR-H 122 mmHg vs. SHR-N 175 mmHg; P less than 0.001; experiment 3: 135 vs. 152 mmHg, respectively; P less than 0.05). Elevations in O2 consumption (VO2) and rectal temperature (Tre) in SHR vs. normotensive [Wistar-Kyoto (WKY)] rats provided evidence that the SHR is a hypermetabolic animal. Thyroid hormonal indices suggested that SHR changed from a low to high thyroid status at a time that rapid blood pressure elevation occurred; however, hypoxia did not influence thyroid status. Acute, significant decrements in VO2 and Tre in SHR-H (experiments 2 and 3) accompanied the attenuation of SBP by hypoxia, whereas large decrements in VO2 and SBP did not occur in hypoxic WKY. Timely administration of moderate hypoxia protects against the development of hypertension in the SHR. This protection may relate to a metabolic adaptation made by the hypoxic SHR.

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NEPHRON NUMBER, RENAL FILTRATION SURFACE AREA AND BLOOD PRESSURE IN F2 HYBRIDS OF A SPONTANEOUSLY HYPERTENSIVE RAT/WISTAR-KYOTO RAT CROSS

Nephrology ◽

10.1046/j.1440-1797.2002.00007-1-120.x ◽

2002 ◽

Vol 7 (1) ◽

pp. A120-A120

Author(s):

Briscoe Ta ◽

Kett Mm ◽

Bertram Jf ◽

Black MJ

Keyword(s):

Blood Pressure ◽

Surface Area ◽

Spontaneously Hypertensive Rat ◽

Nephron Number ◽

Spontaneously Hypertensive ◽

Hypertensive Rat ◽

F2 Hybrids ◽

Wistar Kyoto Rat ◽

Wistar Kyoto ◽

Filtration Surface

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Blood pressure cosegregates with a microsatellite of angiotensin I converting enzyme (ACE) in F2 generation from a cross between original normotensive Wistar-Kyoto rat (WKY) and stroke-prone spontaneously hypertensive rat (SHRSP)

Biochemical and Biophysical Research Communications ◽

10.1016/0006-291x(91)92027-h ◽

1991 ◽

Vol 181 (3) ◽

pp. 941-946 ◽

Cited By ~ 36

Author(s):

Yasuo Nara ◽

Toru Nabika ◽

Katsumi Ikeda ◽

Makoto Sawamura ◽

Jiro Endo ◽

...

Keyword(s):

Blood Pressure ◽

Spontaneously Hypertensive Rat ◽

Converting Enzyme ◽

Angiotensin I ◽

Spontaneously Hypertensive ◽

Angiotensin I Converting Enzyme ◽

Hypertensive Rat ◽

Wistar Kyoto Rat ◽

Wistar Kyoto ◽

F2 Generation

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Experimental study of the effects of hypoxia simulator on osteointegration of titanium prosthesis in osteoporotic rats

BMC Musculoskeletal Disorders ◽

10.1186/s12891-021-04777-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Jiangfeng Liu ◽

Huijun Kang ◽

Jiangfeng Lu ◽

Yike Dai ◽

Fei Wang

Keyword(s):

Signaling Pathway ◽

Control Group ◽

Osteoporotic Bone ◽

Sham Operation ◽

Mrna Levels ◽

Micro Ct ◽

Sprague Dawley ◽

Micro Computed Tomography ◽

Sham Operation Group ◽

Pull Out

Abstract Background Poor osseointegration is the key reason for implant failure after arthroplasty,whether under osteoporotic or normal bone conditions. To date, osseointegration remains a major challenge. Recent studies have shown that deferoxamine (DFO) can accelerate osteogenesis by activating the hypoxia signaling pathway. The purpose of this study was to test the following hypothesis: after knee replacement, intra-articular injection of DFO will promote osteogenesis and osseointegration with a 3D printed titanium prosthesis in the bones of osteoporotic rats. Materials and methods Ninety female Sprague–Dawley rats were used for the experiment. Ten rats were used to confirm the successful establishment of the osteoporosis model: five rats in the sham operation group and five rats in the ovariectomy group. After ovariectomy and knee arthroplasty were performed, the remaining 80 rats were randomly divided into DFO and control groups (n = 40 per group). The two groups were treated by intraarticular injection of DFO and saline respectively. After 2 weeks, polymerase chain reaction (PCR) and immunohistochemistry were used to evaluate the levels of HIF-1a, VEGF, and CD31. HIF-1a and VEGF have been shown to promote angiogenesis and bone regeneration, and CD31 is an important marker of angiogenesis. After 12 weeks, the specimens were examined by micro-computed tomography (micro-CT), biomechanics, and histopathology to evaluate osteogenesis and osseointegration. Results The results of PCR showed that the mRNA levels of VEGF and CD31 in the DFO group were significantly higher than those in the control group. The immunohistochemistry results indicated that positive cell expression of HIF-1a, VEGF, and CD31 in the DFO group was also higher. Compared with the control group, the micro-CT parameters of BMD, BV/TV, TB. N, and TB. Th were significantly higher. The maximal pull-out force and the bone-to-implant contact value were also higher. Conclusions The local administration of DFO, which is used to activate the HIF-1a signaling pathway, can promote osteogenesis and osseointegration with a prosthesis in osteoporotic bone.

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Effect of Yishenjiangyafang on Plasma Metabolomics in Senile Spontaneously Hypertensive Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8868267 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Lei Zhang ◽

Jie Yu ◽

Yingying Liu ◽

Weixing Guo ◽

Yunlun Li

Keyword(s):

Blood Pressure ◽

Treatment Group ◽

Group Treatment ◽

Metabolic Pathways ◽

Spontaneously Hypertensive Rats ◽

Control Group ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Q Exactive ◽

Wistar Kyoto

Objectives. Yishenjiangyafang is a traditional Chinese medicine used to clinically treat hypertension. This study aimed to explore the effect of yishenjiangyafang on plasma metabolomics in senile spontaneously hypertensive rats (SHRs). Methods. Twelve 50-week-old SHR (6 males and 6 females) were randomly divided into two groups: a treatment group, in which rats were intragastrically administered with yishenjiangyafang (10.08 g kg−1·d−1), and a model group, in which all SHRs were administered the same volume of saline. Six age- and gender-matched Wistar–Kyoto (WKY) rats were used as the control group. Treatment was given for 6 days per week and lasted for 8 weeks. Systolic and diastolic blood pressures of the rats were measured with the noninvasive tail artery pressure measurement system. An ultraperformance liquid chromatography quadruple electrostatic field orbit (UPLC-Q-Exactive) was used to determine metabolite changes in the plasma of SHR rats before and after yishenjiangyafang treatment in the treatment group as well as in the model and control groups. Results. After yishenjiangyafang treatment, SHRs had significant lower blood pressure. Using UPLC-Q-Exactive, we identified 26 metabolic targets of yishenjiangyafang in aged SHRs and revealed that yishenjiangyafang targeted four major metabolic pathways, linoleic acid metabolism, glycerophospholipid metabolism, arginine and proline metabolism, and steroid hormone biosynthesis. Conclusion. Yishenjiangyafang decreases the blood pressure of SHRs at least in part through targeting of four major metabolic pathways. Our study illustrates mechanisms underlying the clinical application of yishenjiangyafang in the treatment of hypertensive patients.

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Effects of unilateral/bilateral amputation of the ischiocavernosus muscle in male rats on erectile function and conception

Basic and Clinical Andrology ◽

10.1186/s12610-021-00151-7 ◽

2022 ◽

Vol 32 (1) ◽

Author(s):

Chengren Gou ◽

Tong Liu ◽

Zongping Chen ◽

Zidong Zhou ◽

Tao Song ◽

...

Keyword(s):

Erectile Function ◽

Penile Erection ◽

Female Rats ◽

Male Rats ◽

Control Group ◽

Sham Operation ◽

Sham Operation Group ◽

Ischiocavernosus Muscle ◽

Operation Group ◽

Paired Female

Abstract Background The ischiocavernosus muscle (ICM) encompasses a pair of short pinnate muscles attached to the pelvic ring. The ICM begins at the ischial tuberosity and ends at the crus of the penis while covering the surface of the crus. According to the traditional view, the contraction of the ICM plays an auxiliary role in penile erection. However, we have previously shown that the ICM plays an important role in penile erection through an indirect method of diagnosing erectile dysfunction (ED) caused by ICM injury by observing the infertility of paired female rats. Since intracavernosal pressure (ICP) is the current gold standard for diagnosing ED, this study aimed to amputate unilaterally/bilaterally the ICM to establish an ED model by detecting the ICP, recording the infertility of matching female rats, and comparing the two methods. Results Forty sexually mature adult male rats were selected and randomly divided into the following groups: the control group (n = 10), sham operation group (n = 10), unilateral ischiocavernosus muscle (Uni-ICM) amputation group (n = 10), and bilateral ischiocavernosus muscle (Bi-ICM) amputation group (n = 10). Eighty female reproductive rats were randomly assigned to the above groups at a ratio of 2:1. We evaluated the time to conception for the paired female rats and the effects of unilateral/bilateral severing of the ICM on erectile function. The results showed that the baseline and maximum intracavernosal pressure (ICP) in the control group, sham operation group, Uni-ICM amputation group, and Bi-ICM amputation group were 17.44±2.50 mmHg and 93.51±10.78 mmHg, 17.81±2.81 mmHg and 95.07±10.40 mmHg, 16.73±2.11 mmHg and 83.49±12.38 mmHg, and 14.78±2.78 mmHg and 33.57±6.72 mmHg, respectively, immediately postsurgery. The max ICP in the Bi-ICM amputation group was lower than that in the remaining three groups (all P<0.05). The pregnancy rates were 100, 100, 90, and 0% in the control group, sham operation group, Uni-ICM amputation group, and the Bi-ICM amputation group, respectively. The pregnancy rate in the Bi-ICM amputation group was significantly lower than that in the remaining groups (all P<0.05). The time to conception was approximately 7–10 days later in the Uni-ICM amputation group than in the control and sham groups (all P<0.05). Conclusions Male rats undergoing Bi-ICM amputation may develop permanent ED, which affects their fertility. In contrast, rats undergoing Uni-ICM amputation may experience transient ED.

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