Adrenal and circulating renin-angiotensin system in stroke-prone hypertensive rats.

Kim, Shokei; Tokuyama, Masatoshi; Hosoi, Masayuki; Yamamoto, Kenjiro

doi:10.1161/01.hyp.20.3.280

Cited by 56 publications

(27 citation statements)

References 50 publications

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“…14,15) SHRsp, bred to develop hypertension soon after birth, rapidly present with hypertensive disorders of various organs. [16][17][18] Regarding the kidney, elevation of plasma renin level begins at age 18 weeks 19) and disturbance of renal function from 22-24 weeks. 20) Although many attempts have been made at treating SHRsp with ARBs or CCBs, treatment was often performed before the appearance of hypertensive disorders, and it remains unknown whether these drugs exert renoprotective effects when they administered after the onset of kidney disease.…”

Section: Discussionmentioning

confidence: 99%

Renoprotective Effect of Azelnidipine in Rats

Kurashige

Abe

Furusu

et al. 2008

Biological & Pharmaceutical Bulletin

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To assess whether azelnidipine (AZN) exerts renoprotective effects, 20-week-old adult male stroke-prone spontaneously hypertensive rats (SHRsp) were treated with AZN 10 mg/kg/d (n‫,)6؍‬ olmesartan (OLM) 3 mg/kg/d (n‫,)4؍‬ hydralazine (HYD) 20 mg/kg/d (n‫,)3؍‬ or water (control; n‫.)5؍‬ Each test agent was administered by oral gavage for 12 weeks. Systolic blood pressure (SBP) was measured every 2 weeks and urinary protein excretion (UproV) every 3 weeks. At the age of 32 weeks, the rats were sacrificed and blood and kidneys collected for biochemical, histological, and immunohistochemical studies. All drug treatments significantly (pϽ0.05) reduced SBP, UproV, and blood biochemical parameters such as creatinine, total cholesterol, and blood urea nitrogen. Masson trichrome staining and immunohistochemical staining revealed significant (pϽ0.05) reductions of interstitial fibrosis, collagen type III, nicotinamide-adenine dinucleotide/nicotinamide-adenine dinucleotide phosphate oxidase, and p22 phox and p47 phox components expression in the AZN-and OLM-treated groups in comparison with rats treated with HYD and control animals. ED1, 4-hydroxy-2-nonenal (4-HNE), and heat shock protein (HSP)-47 expression was also reduced in the AZN-and OLM-treated groups versus in HYD and control animals. These results indicate that not only OLM but also AZN exerts renoprotective effects through inhibition of macrophage infiltration and antioxidant activity in SHRsp model of renal injury.

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Section: Discussionmentioning

confidence: 99%

Renoprotective Effect of Azelnidipine in Rats

Kurashige

Abe

Furusu

et al. 2008

Biological & Pharmaceutical Bulletin

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“…1,2 On the other hand, plasma renin activity and plasma angiotensin II (Ang II) levels are not consistently elevated during any given stage of development in SHR. [3][4][5][6][7] Likewise, although plasma Ang II is elevated in stroke-prone SHR, plasma renin, angiotensinogen, and Ang II do not cosegregate with elevated blood pressure. 8,9 It is now recognized that the tissue levels of components of the RAS are more reliable indices of functional activity than are plasma levels.…”

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confidence: 99%

“…18 Likewise, the renal vasculature of SHR have been shown to be hypersensitive to Ang II. 19 -22 There is no agreement, however, as to whether Ang II levels 4,5,7,23 or Ang II receptors 19,24 -28 are altered during the development or maintenance of the hypertension. Young SHR have elevated proximal tubule sodium reabsorption that can be reduced by ACE inhibition, whereas sodium reabsorption from adult SHR proximal tubules is reduced.…”

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confidence: 99%

Kidney Aminopeptidase A and Hypertension, Part I

Healy

Song

1999

Hypertension

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Abstract-Tissue and plasma levels of aminopeptidase A (APA), the principal enzyme that hydrolyzes angiotensin II (Ang II) to angiotensin III, were measured in spontaneously hypertensive rats (SHR) and their normotensive control strain at 3 different ages corresponding to prehypertensive (4 weeks), developing (8 weeks), and established (16 weeks) phases of hypertension. Plasma APA activity was significantly but modestly elevated in SHR at all 3 ages compared with normotensive Wistar-Kyoto rats. Likewise, levels of APA in brain, heart, and adrenal gland were generally, but again only moderately, elevated in SHR at all ages. However, a large increase in APA activity was seen within the kidney in which APA levels were elevated 41%, 51%, and 68% in SHR at 4, 8, and 16 weeks of age, respectively. Kidney APA levels were also significantly increased in immunoblots from 8-and 16-week-old SHR. Glomeruli isolated from 16-week-old SHR had 57% higher APA activity and increased immunoreactivity compared with Wistar-Kyoto rats. To determine whether the increase in kidney APA activity in SHR was related to Ang II levels, SHR were treated for 2 weeks with the angiotensin-converting enzyme inhibitor captopril. Captopril treatment reduced blood pressure to normotensive values and resulted in a 25% reduction in kidney APA activity. These results suggest that APA expression in the kidney may be regulated by activity of the renin-angiotensin system. If so, this would further suggest that upregulation of APA during conditions in which Ang II levels were elevated would have a protective effect against Ang II-mediated cardiovascular diseases, whereas a decrease in APA expression or a failure to upregulate would exacerbate such conditions. (Hypertension. 1999;33:740-745.)

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“…The second is that the local expression of adrenal renin is required for normal ZG function (7,9,10,14,16,26,28,29,31). One of the theories is that local generation of adrenal ANG II mediates the ZG response to increases in potassium and that this is mediated by AT 1 -type angiotensin receptors (14,26,29).…”

Section: Discussionmentioning

confidence: 99%

Renin knockout rat: control of adrenal aldosterone and corticosterone synthesis in vitro and adrenal gene expression

Raff

Gehrand

Bruder

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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The classic renin-angiotensin system is partly responsible for controlling aldosterone secretion from the adrenal cortex via the peptide angiotensin II (ANG II). In addition, there is a local adrenocortical reninangiotensin system that may be involved in the control of aldosterone synthesis in the zona glomerulosa (ZG). To characterize the long-term control of adrenal steroidogenesis, we utilized adrenal glands from renin knockout (KO) rats and compared steroidogenesis in vitro and steroidogenic enzyme expression to wild-type (WT) controls (Dahl S rat). Adrenal capsules (ZG; aldosterone production) and subcapsules [zona reticularis/fasciculata (ZFR); corticosterone production] were separately dispersed and studied in vitro. Plasma renin activity and ANG II concentrations were extremely low in the KO rats. Basal and cAMP-stimulated aldosterone production was significantly reduced in renin KO ZG cells, whereas corticosterone production was not different between WT and KO ZFR cells. As expected, adrenal renin mRNA expression was lower in the renin KO compared with the WT rat. Real-time PCR and immunohistochemical analysis showed a significant decrease in P450aldo (Cyp11b2) mRNA and protein expression in the ZG from the renin KO rat. The reduction in aldosterone synthesis in the ZG of the renin KO adrenal seems to be accounted for by a specific decrease in P450aldo and may be due to the absence of chronic stimulation of the ZG by circulating ANG II or to a reduction in locally released ANG II within the adrenal gland. aldosterone; corticosterone; adrenal cortex; renin; knockout rat ALDOSTERONE IS SYNTHESIZED in the zona glomerulosa (ZG) of the adrenal gland and is stimulated by angiotensin II (ANG II), ACTH, and potassium (5,8,25). Aldosterone is critical in the control of renal sodium and potassium excretion. The classic renal renin-angiotensin-aldosterone system (RAAS) is well known as a major regulator of sodium and potassium balance. However, it has been known for decades that the adrenal cortex also expresses a local RAAS that operates independently of the renal RAAS (2,7,9,14,16,26,28). One theory is that adrenal renin-generated ANG II mediates the ZG response to increases in plasma potassium, and this is mediated by expression of the angiotensin AT 1 receptor (5,9,14,26,29).The development of the renin knockout (KO) rat provides a unique opportunity to begin to evaluate these phenomena (13).In the current study, we have begun this process by evaluating the aldosterone and corticosterone response to cAMP in vitro by the measurement of adrenal steroidogenic gene expression and by morphological examination of adrenal zonation by immunohistochemical analysis of the two major late-pathway steroidogenic enzymes: P450aldo (CYP11B2) that mediates the conversion of corticosterone to aldosterone in the ZG and P45011␤ (CYP11B1) that mediates corticosterone production in the zona fasciculata/reticularis (ZFR) (8). MATERIALS AND METHODS Generation of the renin KO rat. All experiments were approved by the Medical College o...

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Adrenal and circulating renin-angiotensin system in stroke-prone hypertensive rats.

Cited by 56 publications

References 50 publications

Renoprotective Effect of Azelnidipine in Rats

Renoprotective Effect of Azelnidipine in Rats

Kidney Aminopeptidase A and Hypertension, Part I

Renin knockout rat: control of adrenal aldosterone and corticosterone synthesis in vitro and adrenal gene expression

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