Effects of Long-term Treatment with Candesartan on Organ Damages in Sinoaortic Denervated Rats

Xie, He-Hui; Jian-guo, Liu; Su, Ding‐Feng

doi:10.1097/00005344-200302000-00023

Cited by 23 publications

(24 citation statements)

References 17 publications

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“…Systolic BP (SBP), diastolic BP (DBP) and heart period (HP) of rats were continuously recorded using a previously described technique [9,10] . Briefly, rats were anesthetized with a combination of ketamine (40 mg/kg) and diazepam (6 mg/kg).…”

Section: Bp Measurementmentioning

confidence: 99%

Synergism of irbesartan and amlodipine on hemodynamic amelioration and organ protection in spontaneously hypertensive rats

et al. 2011

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Aim: To investigate the synergism of low-doses of amlodipine and irbesartan on reduction of blood pressure variability (BPV), amelioration of baroreflex sensitivity (BRS) and organ protection in spontaneously hypertensive rats (SHR). Methods: The rats were administered amlodipine (1 mg·kg -1 ·d -1 ) alone, irbesartan (10 mg·kg -1 ·d -1 ) alone, or the combination of the two drugs for 4 months. The drugs were mixed into the rat chow. Blood pressure (BP) was continuously monitored in conscious animals. After the determination of BRS, the rats were killed for morphological evaluation of organ damages. Results: The combination of low-dose irbesartan and amlodipine had statistically significant synergism on reduction of BP and BPV, amelioration of BRS and organ protection in SHR. Multiple regression analysis showed that the decrease in left ventricular hypertrophy was associated with the decrease in systolic BPV (r=0.665, P<0.01); the decrease in aortic hypertrophy was associated with the increase in BRS (r=0.656, P<0.01); and the amelioration in renal lesion was associated with the increase in BRS (r=0.763, P<0.01) and the decrease in systolic BPV (r=0.706, P<0.01). Conclusion: Long-term treatment with a combination of low-doses of amlodipine and irbesartan showed significant synergism on reduction of BP and BPV, restoration of BRS and organ protection in SHR. Besides BP reduction, the enhancement of BRS and reduction of BPV might contribute to the organ protection.

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Section: Bp Measurementmentioning

confidence: 99%

Synergism of irbesartan and amlodipine on hemodynamic amelioration and organ protection in spontaneously hypertensive rats

et al. 2011

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“…39 However, it remains unknown whether the inhibitory effect of candesartan on cardiac remodeling was attributable to the direct AT1R blocking or simply to its depressor effect. In this study, a subdepressor dose of candesartan prevented the SAD-induced aggravation of myocardial remodeling and LV dysfunction in SHRs without changing the magnitude of BPV ( Figure 4 and Table 2).…”

Section: Kudo Et Al Bp Variability and Cardiac Inflammation 835mentioning

confidence: 99%

Exaggerated Blood Pressure Variability Superimposed on Hypertension Aggravates Cardiac Remodeling in Rats via Angiotensin II System-Mediated Chronic Inflammation

et al. 2009

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Abstract-Hypertensive patients with large blood pressure variability (BPV) have aggravated end-organ damage.However, the pathogenesis remains unknown. We investigated whether exaggerated BPV aggravates hypertensive cardiac remodeling and function by activating inflammation and angiotensin II-mediated mechanisms. A model of exaggerated BPV superimposed on chronic hypertension was created by performing bilateral sinoaortic denervation (SAD) in spontaneously hypertensive rats (SHRs). SAD increased BPV to a similar extent in Wistar Kyoto rats and SHRs without significant changes in mean blood pressure. SAD aggravated left ventricular and myocyte hypertrophy and myocardial fibrosis to a greater extent and impaired left ventricular systolic function in SHRs. SAD induced monocyte chemoattractant protein-1, transforming growth factor-␤, and angiotensinogen mRNA upregulations and macrophage infiltration of the heart in SHRs. The effects of SAD on cardiac remodeling and inflammation were much smaller in Wistar Kyoto rats compared with SHRs. Circulating levels of norepinephrine, the active form of renin, and inflammatory cytokines were not affected by SAD in Wistar Kyoto rats and SHRs. A subdepressor dose of candesartan abolished the SAD-induced left ventricular/myocyte hypertrophy, myocardial fibrosis, macrophage infiltration, and inductions of monocyte chemoattractant protein-1, transforming growth factor-␤, and angiotensinogen and subsequently prevented systolic dysfunction in SHRs with SAD. These findings suggest that exaggerated BPV induces chronic myocardial inflammation and thereby aggravates cardiac remodeling and systolic function in hypertensive hearts. The cardiac angiotensin II system may play a role in the pathogenesis of cardiac remodeling and dysfunction induced by a combination of hypertension and exaggerated BPV. Key Words: blood pressure variability Ⅲ hypertension Ⅲ inflammation Ⅲ angiotensin II Ⅲ cardiac hypertrophy T he goal of hypertension treatment is not only to reduce blood pressure (BP) levels but also to prevent cardiovascular events. Among hypertensive patients, patients with large BP variability (BPV) have more advanced end-organ damage, such as left ventricular (LV) hypertrophy and carotid atherosclerosis. [1][2][3][4][5][6][7] Recent studies have shown that exaggerated BPV is a risk factor for cardiovascular events in hypertensive patients, 8 -10 independent of diurnal BP changes. 11 An exaggerated BPV is a characteristic feature of hypertension, especially in the elderly and in patients with carotid atherosclerosis. 12-14 However, little is known about the mechanism underlying the aggravation of end-organ damage induced by a combination of hypertension and large BPV aggravates.Our recent studies have shown that perivascular inflammation plays a pivotal role in hypertensive cardiac remodeling, especially in myocardial fibrosis (for review see References 15 and 16): in Wistar Kyoto rats (WKYs) with suprarenal aortic constriction, BP elevation induces perivascular inflammation characterized by ...

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“…In off-line analysis, the mean values of these parameters over a 24-h period were calculated and served as SBP, DBP and HP, respectively. The standard deviation values of these parameters over the 24-h period were calculated and defined as systolic blood pressure variability (SBPV), diastolic blood pressure variability (DBPV) and heart period variability (HPV), respectively [6,9,10,12].…”

Section: Haemodynamic Measurementmentioning

confidence: 99%

Blood pressure variability is more important than blood pressure level in determination of end-organ damage in rats

Miao

Xie²,

Zhan³

et al. 2006

Journal of Hypertension

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Effects of Long-term Treatment with Candesartan on Organ Damages in Sinoaortic Denervated Rats

Cited by 23 publications

References 17 publications

Synergism of irbesartan and amlodipine on hemodynamic amelioration and organ protection in spontaneously hypertensive rats

Synergism of irbesartan and amlodipine on hemodynamic amelioration and organ protection in spontaneously hypertensive rats

Exaggerated Blood Pressure Variability Superimposed on Hypertension Aggravates Cardiac Remodeling in Rats via Angiotensin II System-Mediated Chronic Inflammation

Blood pressure variability is more important than blood pressure level in determination of end-organ damage in rats

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