Differential evolution of blood pressure and renal lesions after RAS blockade in Lyon hypertensive rats

2002 ◽  
Vol 283 (5) ◽  
pp. R1041-R1045 ◽  
Author(s):  
Delphine Bertram ◽  
Nelly Blanc-Brunat ◽  
Jean Sassard ◽  
Ming Lo

The present work aimed to assess, in Lyon hypertensive (LH) rats, whether an early and prolonged inhibition of the renin-angiotensin system (RAS) could result in a blood pressure (BP) lowering and nephroprotection that persist after its withdrawal. Male LH rats received orally from 3 to 12 wk of age either an angiotensin-converting enzyme inhibitor perindopril at the doses of 0.4 and 3 mg · kg−1· day−1or an AT1receptor antagonist losartan at the dose of 10 mg · kg−1· day−1. BP, histological changes in the kidney, and urinary protein excretion were examined during and 10 wk after cessation of the treatments. Both perindopril and losartan decreased BP, prevented renal lesions, and limited urinary protein excretion. After cessation of the treatment, BP returned to the level of never-treated LH rats in rats having received 3 mg · kg−1· day−1of perindopril while it remained slightly lower in those treated with 0.4 mg · kg−1· day−1of perindopril or with losartan. This lack of marked persistent antihypertensive effect contrasted with a durable decrease in urinary protein excretion and improvement of the renal histological lesions. In conclusion, it is possible to separate the BP-lowering effects of RAS blockade from those on glomerulosclerosis and urinary protein excretion.

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Annie L Bell ◽  
Weijian A Shao ◽  
Akemi Katsurada ◽  
Ryosuke Sato ◽  
L Gabriel G NAVAR

Despite growing evidence of sex differences in the progression of hypertension, there are no guidelines that differentiate treatment between men and women. Intrarenal renin-angiotensin system (RAS) activation and tissue injury in 2-kidney, 1-clip (2K1C) hypertensive rats have been characterized in previous studies of male but not female rats. To evaluate possible sex differences in response to renovascular hypertension, urinary angiotensinogen (uAGT) excretion, systolic blood pressure (BP), urinary protein excretion, and renal function were assessed in female rats.Female (n=8) and male (n=6) rats underwent placement of a 0.2 mm clip on the left renal artery to simulate unilateral renal artery stenosis. BP was measured by tail-cuff plethysmography, and clearance studies were conducted in anesthetized rats to assess renal function. Urine protein concentration was determined by pyrogallol red method. uAGT was measured by ELISA as an index of intrarenal RAS activity. Systolic BP increased from 120±1 to 176±8 mmHg, and urinary protein excretion reached 20.2±5.6 mg/day in female rats. Although uAGT excretion increased from 13.2±7.7 ng/day to 74.1±29.9 ng/day in female rats, male rats had a significantly higher uAGT excretion of 1572.6±750 ng/day. Nonclipped kidneys exhibited more uAGT excretion compared to clipped kidneys, consistent with previous findings in males. Although 2K1C female rats demonstrate significantly lower renal function than sham females, they show more preserved renal function than male rats. Female rats also demonstrate significantly lower increases in systolic BP and urinary protein excretion compared to male rats. The data support substantial sex-dependent differences in renal responses to unilateral renal artery stenosis. The results show substantial increases in systolic BP, uAGT, and urinary protein excretion and decreased renal function after renal artery clipping in females, but the magnitude of the changes is markedly lower than in males. Nonclipped kidneys of both sexes exhibit greater uAGT excretion than clipped kidneys. Notably, females show less augmentation of the intrarenal RAS compared to male rats in renovascular hypertension.


1982 ◽  
Vol 243 (1) ◽  
pp. E48-E51 ◽  
Author(s):  
H. Suzuki ◽  
M. Handa ◽  
K. Kondo ◽  
T. Saruta

The role of the renin-angiotensin system in the regulation of the blood pressure of dexamethasone-treated rats (Dex) was evaluated using saralasin, an angiotensin II antagonist, and SQ 14225 (SQ) (d-3-mercapto-2-methylpropranoyl-1-proline), an angiotensin-converting enzyme inhibitor. During a 7-day period blood pressure rose 65 +/- 10 mmHg (P less than 0.001) in Dex with no significant changes in plasma renin activity. Concurrent administration of dexamethasone and SQ attenuated the elevation of blood pressure (P less than 0.05). In the conscious, freely moving state, intravenous injection of SQ (10, 30, 100 micrograms/kg) reduced blood pressure of DEX in a dose-dependent manner (P less than 0.05). Also, intravenous injection of saralasin (10 micrograms.kg-1 . min-1) reduced blood pressure significantly (P less than 0.01). Bilateral nephrectomy abolished the effects of saralasin and SQ on blood pressure in Dex. These results indicate that the elevation of blood pressure in DEX depends partially on the renin-angiotensin system.


1983 ◽  
Vol 245 (6) ◽  
pp. H1013-H1018 ◽  
Author(s):  
H. Takahashi ◽  
K. Takeda ◽  
H. Ashizawa ◽  
A. Inoue ◽  
S. Yoneda ◽  
...  

Central effects of hydrocortisone were investigated by injecting it intracerebroventricularly (icv) while recording blood pressure and heart rate in awake rats. Dose-dependent increases in both blood pressure and heart rate occurred following injections of hydrocortisone. Pretreatment by icv injections of the angiotensin II antagonist, [Sar1-Ile8]angiotensin II, completely abolished vasopressor responses to subsequent injections of hydrocortisone. When rats were later anesthetized with urethan to allow recording of abdominal sympathetic nerve activity, hydrocortisone produced vasopressor responses accompanied by corresponding increases in sympathetic nerve firing, which were also abolished by central pretreatment with either [Sar1-Ile8]angiotensin II or angiotensin I converting-enzyme inhibitor, captopril. These results indicate that centrally administered hydrocortisone stimulates the brain renin-angiotensin system to produce vasopressor responses by increasing sympathetic nerve firing.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Verónica Guarner-Lans ◽  
Elizabeth Soria-Castro ◽  
Rocío Torrico-Lavayen ◽  
Araceli Patrón-Soberano ◽  
Karla G. Carvajal-Aguilera ◽  
...  

The role of the renin-angiotensin system (RAS) in blood pressure regulation in MS during aging is unknown. It participates in metabolic syndrome (MS) and aging regulating vascular tone and remodeling. RAS might participate in a compensatory mechanism decreasing blood pressure and allowing MS rats to reach 18 months of age and it might form part of therapeutical procedures to ameliorate MS. We studied histological changes and distribution of RAS receptors in aortas of MS aged rats. Electron microscopy images showed premature aging in MS since the increased fibrosis, enlarged endothelium, and invasion of this layer by muscle cells that was present in control 18-month-old aortas were also found in 6-month-old aortas from MS rats. AT1, AT2, and Mas receptors mediate the effects of Ang II and Ang 1-7, respectively. Fluorescence from AT2 decreased with age in control and MS aortas, while fluorescence of AT1 increased in aortas from MS rats at 6 months and diminished during aging. Mas expression increased in MS rats and remained unchanged in control rats. In conclusion, there is premature aging in the aortas from MS rats and the elevated expression of Mas receptor might contribute to decrease blood pressure during aging in MS.


2016 ◽  
Vol 203 ◽  
pp. 98-103 ◽  
Author(s):  
Konstantinos Aznaouridis ◽  
Charalambos Vlachopoulos ◽  
Konstantina Masoura ◽  
Panagiota Pietri ◽  
Gregory Vyssoulis ◽  
...  

2018 ◽  
Vol 70 (1) ◽  
Author(s):  
Justin C. Hunt ◽  
Kenneth A. Davis ◽  
Max G. Sanderford

Abstract Salination of freshwater (FW) bodies has the potential to affect homeostatic regulation of osmotic and volume balance in FW organisms. The renin-angiotensin system (RAS) plays an important role in volume balance by maintaining blood pressure in marine and seawater acclimated euryhaline fish, but little is known about the RAS in FW adapted fish. The purpose of the present study was to first determine if the FW channel catfish (Ictalurus punctatus), demonstrates evidence of a functional RAS. Channel catfish (n = 6) were implanted with a catheter in the dorsal aorta to measure dorsal aortic pressure (PDA) and infuse drugs. Infusion of [Asn1,Val5,Asn9]-angiotensin I (ANGI) at 100, 400, and 1000 ng/kg significantly increased PDA in a dose dependent manner (P < 0.05). Pretreatment with 2 mg/kg of the angiotensin converting enzyme inhibitor, Captopril (CAP), essentially eliminated the pressor response to the highest dose of ANGI (P < 0.05). Finally, infusion of 400 ng/kg [Asn1,Val5]-angiotensin II (ANGII) significantly increased PDA from baseline (P < 0.05). The results suggest that channel catfish appear to have an operational RAS and may serve as a suitable model in which to study the role of ANGII in blood pressure regulation in FW adapted fish.


1999 ◽  
Vol 160 (3) ◽  
pp. 351-363 ◽  
Author(s):  
NJ Bernier ◽  
H Kaiya ◽  
Y Takei ◽  
SF Perry

The individual contributions of, and potential interactions between, the renin-angiotensin system (RAS) and the humoral adrenergic stress response to blood pressure regulation were examined in rainbow trout. Intravenous injection of the smooth muscle relaxant, papaverine (10 mg/kg), elicited a transient decrease in dorsal aortic blood pressure (PDA) and systemic vascular resistance (RS), and significant increases in plasma angiotensin II (Ang II) and catecholamine concentrations. Blockade of alpha-adrenoceptors before papaverine treatment prevented PDA and RS recovery, had no effect on the increase in plasma catecholamines, and resulted in greater plasma Ang II concentrations. Administration of the angiotensin-converting enzyme inhibitor, lisinopril (10(-4) mol/kg), before papaverine treatment attenuated the increases in the plasma concentrations of Ang II, adrenaline, and noradrenaline by 90, 79, and 40%, respectively and also prevented PDA and RS recovery. By itself, lisinopril treatment caused a gradual and sustained decrease in PDA and RS, and reductions in basal plasma Ang II and adrenaline concentrations. Bolus injection of a catecholamine cocktail (4 nmol/kg noradrenaline plus 40 nmol/kg adrenaline) in the lisinopril+papaverine-treated trout, to supplement their circulating catecholamine concentrations and mimic those observed in fish treated only with papaverine, resulted in a temporary recovery in PDA and RS. These results indicate that the RAS and the acute humoral adrenergic response are both recruited during an acute hypotensive stress, and have important roles in the compensatory response to hypotension in rainbow trout. However, whereas the contribution of the RAS to PDA recovery is largely indirect and relies on an Ang II-mediated secretion of catecholamines, the contribution from the adrenergic system is direct and relies at least in part on plasma catecholamines.


2010 ◽  
Vol 203 (4) ◽  
pp. 364.e6-364.e12 ◽  
Author(s):  
Ekaterine Tskitishvili ◽  
Hitomi Nakamura ◽  
Yukiko Kinugasa-Taniguchi ◽  
Takeshi Kanagawa ◽  
Koichiro Shimoya ◽  
...  

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