Abnormal renal medullary response to angiotensin II in SHR is corrected by long-term enalapril treatment

2001 ◽  
Vol 280 (4) ◽  
pp. R1076-R1084 ◽  
Author(s):  
Stephen A. W. Dukacz ◽  
Ming-Guo Feng ◽  
Lu-Fang Yang ◽  
Robert M. K. W. Lee ◽  
Robert L. Kline
Keyword(s):  
Renal Medulla ◽  
Term Treatment ◽  
Ang Ii ◽  
Doppler Flowmetry ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Long Term Treatment ◽  
Renal Medullary Blood Flow ◽  
Wistar Kyoto

This study tested the hypotheses that renal medullary blood flow (MBF) in spontaneously hypertensive rats (SHR) has enhanced responsiveness to angiotensin (ANG) II and that long-term treatment with enalapril can correct this. MBF, measured by laser Doppler flowmetry in anesthetized rats, was not altered significantly by ANG II in Wistar-Kyoto (WKY) rats, but was reduced dose dependently (25% at 50 ng · kg−1 · min−1) in SHR. Infusion of N G-nitro-l-arginine methyl ester (l-NAME) into the renal medulla unmasked ANG II sensitivity in WKY rats while l-arginine given into the renal medulla abolished the responses to ANG II in SHR. In 18- to 19-wk-old SHR treated with enalapril (25 mg · kg−1 · day−1 when 4 to 14 wk old), ANG II did not alter MBF significantly, but sensitivity to ANG II was unmasked after l-NAME was infused into the renal medulla. Endothelium-dependent vasodilation (assessed with aortic rings) was significantly greater in treated SHR when compared with that in control SHR. These results indicate that MBF in SHR is sensitive to low-dose ANG II and suggest that this effect may be due to an impaired counterregulatory effect of nitric oxide. Long-term treatment with enalapril improves endothelium-dependent vascular relaxation and decreases the sensitivity of MBF to ANG II. These effects may be causally related to the persistent antihypertensive action of enalapril in SHR.

Effect of long-term treatment with urocortin on the activity of somatic angiotensin-converting enzyme in spontaneously hypertensive rats

2010 ◽  
Vol 88 (2) ◽  
pp. 168-176 ◽  
Author(s):  
Cui Yang ◽  
Xiuxia Liu ◽  
Shengnan Li
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Spontaneously Hypertensive Rats ◽  
Term Treatment ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Long Term Treatment ◽  
Ace Activity

Our previous acute study on urocortin (Ucn) demonstrated that Ucn altered serum and tissue angiotensin-converting enzyme (ACE) activity in rats. Therefore, the present investigation was designed to explore the effect of long-term treatment with Ucn on somatic ACE (sACE) and other components of the renin–angiotensin system (RAS). After 8 weeks of intravenous administration of Ucn in spontaneously hypertensive rats (SHR), serum and tissue sACE, angiotensin II (Ang II), nitric oxide (NO), Ang-(1–7), and tissue chymase activities were evaluated. RT-PCR analysis was performed to determine the quantity of tissue sACE mRNA. Serum sACE activity was reduced by Ucn, although tissue sACE activity and tissue sACE mRNA were elevated. Chymase activity was observed to be enhanced by Ucn, whereas the ACE inhibitor enalapril failed to influence chymase. Serum and tissue Ang II activity was reduced, but NO and Ang-(1–7) production was increased in a concentration-dependent manner after Ucn treatment. Meanwhile, a significant decrease of the systolic blood pressure (SBP) was observed after the long-term Ucn administration, and there was a significant positive correlation (r2 = 0.6993) between serum ACE activity and SBP. Pretreatment with the corticotropin-releasing factor (CRF) blocker astressin and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway blocker PD98059 abolished these effects of Ucn. Our findings further support the hypothesis that the changes of sACE activity and the production of other RAS components may play roles in the vasodilatory property of Ucn via the activation of the ERK1/2 pathway.

Enhanced renal sensitivity of the spontaneously hypertensive rat to urotensin II

2008 ◽  
Vol 295 (4) ◽  
pp. F1239-F1247 ◽  
Author(s):  
Alaa E. S. Abdel-Razik ◽  
Richard J. Balment ◽  
Nick Ashton
Keyword(s):  
Renal Function ◽  
Spontaneously Hypertensive Rat ◽  
Renal Medulla ◽  
Fractional Excretion ◽  
Urotensin Ii ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Hypertensive Rat ◽  
Fractional Excretion Of Sodium ◽  
Wistar Kyoto

Urotensin II (UII) has been implicated widely in cardiovascular disease. The mechanism(s) through which it contributes to elevated blood pressure is unknown, but its emerging role as a regulator of mammalian renal function suggests that the kidney might be involved. The aim of this study was to determine the effect of UII on renal function in the spontaneously hypertensive rat (SHR). UII infusion (6 pmol·min−1·100 g body wt−1) in anesthetized SHR and control Wistar-Kyoto (WKY) rats produced marked reductions in glomerular filtration rate (ΔGFR WKY, n = 7, −0.3 ± 0.1 vs. SHR, n = 7, −0.6 ± 0.1 ml·min−1·100 g body wt−1, P = 0.03), urine flow, and sodium excretion rates, which were greater in SHR by comparison with WKY rats. WKY rats also showed an increase in fractional excretion of sodium (ΔFENa; +0.6 ± 0.1%, P = 0.02) in contrast to SHR in which no such change was observed (ΔFENa −0.6 ± 0.2%). Blockade of the UII receptor (UT), and thus endogenous UII activity, with urantide evoked an increase in GFR which was greater in SHR (+0.3 ± 0.1) compared with WKY rats (+0.1 ± 0.1 ml·min−1·100 g body wt−1, P = 0.04) and was accompanied by a diuresis and natriuresis. UII and UT mRNA expression were greater in the renal medulla than the cortex of both strains; however, expression levels were up to threefold higher in SHR tissue. SHR are more sensitive than WKY to UII, which acts primarily to lower GFR thus favoring salt retention in this model of hypertension.

scholarly journals Long‐term Treatment with Kefir Probiotics Ameliorates Cardiac Function in Spontaneously Hypertensive Rats

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Mirian Almeida Silva‐Cutini ◽  
Simone Alves Almeida ◽  
Andrews Marques Nascimento ◽  
Glaucia Rodrigues Abreu ◽  
Nazaré Souza Bissoli ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Spontaneously Hypertensive Rats ◽  
Term Treatment ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Long Term Treatment

Long-term captopril treatment restores natriuresis after carotid baroreceptor activation in the SHR

1997 ◽  
Vol 273 (1) ◽  
pp. R70-R79
Author(s):  
J. P. Valentin ◽  
S. A. Mazbar ◽  
M. H. Humphreys
Keyword(s):  
Renal Plasma Flow ◽  
Renal Nerves ◽  
Sprague Dawley ◽  
Wky Rats ◽  
Sprague Dawley Rats ◽  
Long Term Treatment ◽  
Bilateral Carotid ◽  
Wistar Kyoto ◽  
Captopril Treatment

In anesthetized Sprague-Dawley rats, intermittent bilateral carotid artery traction (BilCAT) caused a transient decrease in mean arterial pressure (MAP) of 28 +/- 3 mmHg and led to a progressive increase in sodium excretion (UNaV) that nearly doubled 45-90 min after initiation of the repetitive application of BilCAT (P < 0.001). This natriuresis was accompanied by an increase in glomerular filtration rate (GFR) from 2.70 +/- 0.3 to 3.2 +/- 0.3 ml/min (P < 0.001), no change in renal plasma flow [clearance of p-aminohippurate (PAH)], and an increase in the fractional excretion of lithium. Rats with bilateral renal denervation exhibited neither natriuresis nor an increase in GFR in response to BilCAT despite similar vasodepression caused by the maneuver. Normotensive Wistar-Kyoto (WKY) rats responded to BilCAT like Sprague-Dawley rats, whereas spontaneously hypertensive rats (SHR) exhibited an exaggerated vasodepressor response to BilCAT (-51 +/- 3 mmHg) without increasing either UNaV or GFR. Separate groups of WKY and SHR were treated from 4 wk of age with captopril added to the drinking water at a concentration of 1 g/l. At 12-14 wk, both groups had lower MAP compared with untreated animals. Captopril treatment did not alter either the natriuretic response or the increase in GFR seen in untreated WKY after BilCAT, and the maneuver produced equivalent degrees of vasodepression as in controls. However, treated SHR now responded to BilCAT with increases in both UNaV and GFR that closely resembled the responses seen in Sprague-Dawley and WKY rats. These results suggest that BilCAT produces natriuresis through a pathway dependent on the renal nerves. This pathway does not function in untreated SHR despite similar vasodepression. Long-term treatment with captopril restores this reflex pathway in SHR, lending support to the concept that angiotensin II is critically linked to heightened sympathetic nerve activity and abnormal sodium metabolism in this strain.

Renal medullary nitric oxide deficit of Dahl S rats enhances hypertensive actions of angiotensin II

2002 ◽  
Vol 283 (1) ◽  
pp. R266-R272 ◽  
Author(s):  
Mátyás Szentiványi ◽  
Ai-Ping Zou ◽  
David L. Mattson ◽  
Paulo Soares ◽  
Carol Moreno ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Intravenous Infusion ◽  
Renal Medulla ◽  
Brown Norway ◽  
Ang Ii ◽  
Outer Medulla ◽  
Doppler Flowmetry ◽  
Medullary Blood Flow ◽  
Induced Hypertension ◽  
Renal Medullary Blood Flow

Studies were designed to examine the hypothesis that the renal medulla of Dahl salt-sensitive (Dahl S) rats has a reduced capacity to generate nitric oxide (NO), which diminishes the ability to buffer against the chronic hypertensive effects of small elevations of circulating ANG II. NO synthase (NOS) activity in the outer medulla of Dahl S rats (arginine-citrulline conversion assay) was significantly reduced. This decrease in NOS activity was associated with the downregulation of protein expression of NOS I, NOS II, and NOS III isoforms in this region as determined by Western blot analysis. In anesthetized Dahl S rats, we observed that a low subpressor intravenous infusion of ANG II (5 ng · kg−1 · min−1) did not increase the concentration of NO in the renal medulla as measured by a microdialysis with oxyhemoglobin trapping technique. In contrast, ANG II produced a 38% increase in the concentration of NO (87 ± 8 to 117 ± 8 nmol/l) in the outer medulla of Brown-Norway (BN) rats. The same intravenous dose of ANG II reduced renal medullary blood flow as determined by laser-Doppler flowmetry in Dahl S, but not in BN rats. A 7-day intravenous ANG II infusion at a dose of 3 ng · kg−1 · min−1 did not change mean arterial pressure (MAP) in the BN rats but increased MAP in Dahl S rats from 120 ± 2 to 138 ± 2 mmHg ( P< 0.05). ANG II failed to increase MAP after NO substrate was provided by infusion of l-arginine (300 μg · kg−1 · min−1) into the renal medulla of Dahl S rats. Intravenous infusion ofl-arginine at the same dose had no effect on the ANG II-induced hypertension. These results indicate that an impaired NO counterregulatory system in the outer medulla of Dahl S rats makes them more susceptible to the hypertensive actions of small elevations of ANG II.

scholarly journals REDUCED ADRENAL AMINE SYNTHESIS IN SPONTANEOUSLY HYPERTENSIVE RATS AFTER LONG-TERM TREATMENT WITH PROPRANOLOL

1977 ◽  
Vol 61 (2) ◽  
pp. 318-320 ◽  
Author(s):  
B. ÅBLAD ◽  
O. ALMGREN ◽  
A. CARLSSON ◽  
M. HENNING ◽  
J. JONASSON ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Term Treatment ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Long Term Treatment

Effects of Long-Term Treatment with Candesartan on Hemodynamics and Organ Damage in Spontaneously Hypertensive Rats

2005 ◽  
Vol 19 (6) ◽  
pp. 391-397 ◽  
Author(s):  
He-Hui Xie ◽  
Yuan-Yuan Chen ◽  
Chao-Yu Miao ◽  
Fu-Ming Shen ◽  
Ding-Feng Su
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Organ Damage ◽  
Term Treatment ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Long Term Treatment
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