Angiotensin II Receptor Modulation of Renal Vascular Resistance and Neurotransmission in Young and Adult Spontaneously Hypertensive Rats

Stegbauer, Johannes; Vonend, Oliver; Oberhauser, Vitus; Sellin, Lorenz; Rump, Lars Christian

doi:10.1159/000081020

Cited by 13 publications

(10 citation statements)

References 29 publications

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“…Another important finding is that plasma renin activity is increased in adult rats, suggesting that the RAS activation is due to the well-described neurogenic hypertension in SHR31. This RAS activation may not be essential during the adaptation to hypertension, but it must be essential in a late process, either related to heart failure32 or to vascular injury 33…”

Section: Discussionmentioning

confidence: 99%

Hemodynamic, Morphometric and Autonomic Patterns in Hypertensive Rats - Renin-Angiotensin System Modulation

Zamo¹,

Lacchini²,

Mostarda³

et al. 2010

Clinics

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BACKGROUND:Spontaneously hypertensive rats develop left ventricular hypertrophy, increased blood pressure and blood pressure variability, which are important determinants of heart damage, like the activation of renin-angiotensin system.AIMS:To investigate the effects of the time-course of hypertension over 1) hemodynamic and autonomic patterns (blood pressure; blood pressure variability; heart rate); 2) left ventricular hypertrophy; and 3) local and systemic Renin-angiotensin system of the spontaneously hypertensive rats.METHODS:Male spontaneously hypertensive rats were randomized into two groups: young (n=13) and adult (n=12). Hemodynamic signals (blood pressure, heart rate), blood pressure variability (BPV) and spectral analysis of the autonomic components of blood pressure were analyzed. LEFT ventricular hypertrophy was measured by the ratio of LV mass to body weight (mg/g), by myocyte diameter (μm) and by relative fibrosis area (RFA, %). ACE and ACE2 activities were measured by fluorometry (UF/min), and plasma renin activity (PRA) was assessed by a radioimmunoassay (ng/mL/h). Cardiac gene expressions of Agt, Ace and Ace2 were quantified by RT-PCR (AU).RESULTS:The time-course of hypertension in spontaneously hypertensive rats increased BPV and reduced the alpha index in adult spontaneously hypertensive rats. Adult rats showed increases in left ventricular hypertrophy and in RFA. Compared to young spontaneously hypertensive rats, adult spontaneously hypertensive rats had lower cardiac ACE and ACE2 activities, and high levels of PRA. No change was observed in gene expression of Renin-angiotensin system components.CONCLUSIONS:The observed autonomic dysfunction and modulation of Renin-angiotensin system activity are contributing factors to end-organ damage in hypertension and could be interacting. Our findings suggest that the management of hypertensive disease must start before blood pressure reaches the highest stable levels and the consequent established end-organ damage is reached.

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Section: Discussionmentioning

confidence: 99%

Hemodynamic, Morphometric and Autonomic Patterns in Hypertensive Rats - Renin-Angiotensin System Modulation

Zamo¹,

Lacchini²,

Mostarda³

et al. 2010

Clinics

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“…In mice and rat kidney, angiotensin II regulates vascular resistance and enhances neurotransmitter release solely by activation of post-and presynaptic AT 1 -receptors, respectively (27,30). On the other hand, NO serves as a potent vasodilator, has an important role in the maintenance of vascular tone, and seems to counteract angiotensin II-mediated hemodynamic effects (4).…”

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confidence: 99%

Endothelial nitric oxide synthase is predominantly involved in angiotensin II modulation of renal vascular resistance and norepinephrine release

Stegbauer

Kuczka²,

Vonend³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Nitric oxide (NO) is mainly generated by endothelial NO synthase (eNOS) or neuronal NOS (nNOS). Recent studies indicate that angiotensin II generates NO release, which modulates renal vascular resistance and sympathetic neurotransmission. Experiments in wild-type [eNOS(+/+) and nNOS(+/+)], eNOS-deficient [eNOS(-/-)], and nNOS-deficient [nNOS(-/-)] mice were performed to determine which NOS isoform is involved. Isolated mice kidneys were perfused with Krebs-Henseleit solution. Endogenous norepinephrine release was measured by HPLC. Angiotensin II dose dependently increased renal vascular resistance in all mice species. EC(50) and maximal pressor responses to angiotensin II were greater in eNOS(-/-) than in nNOS(-/-) and smaller in wild-type mice. The nonselective NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 0.3 mM) enhanced angiotensin II-induced pressor responses in nNOS(-/-) and wild-type mice but not in eNOS(-/-) mice. In nNOS(+/+) mice, 7-nitroindazole monosodium salt (7-NINA; 0.3 mM), a selective nNOS inhibitor, enhanced angiotensin II-induced pressor responses slightly. Angiotensin II-enhanced renal nerve stimulation induced norepinephrine release in all species. L-NAME (0.3 mM) reduced angiotensin II-mediated facilitation of norepinephrine release in nNOS(-/-) and wild-type mice but not in eNOS(-/-) mice. 7-NINA failed to modulate norepinephrine release in nNOS(+/+) mice. (4-Chlorophrnylthio)guanosine-3', 5'-cyclic monophosphate (0.1 nM) increased norepinephrine release. mRNA expression of eNOS, nNOS, and inducible NOS did not differ between mice strains. In conclusion, angiotensin II-mediated effects on renal vascular resistance and sympathetic neurotransmission are modulated by NO in mice. These effects are mediated by eNOS and nNOS, but NO derived from eNOS dominates. Only NO derived from eNOS seems to modulate angiotensin II-mediated renal norepinephrine release.

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“…10 Our recent studies also show that, in vivo, a chronic infusion of noradrenaline increases BSC-1 expression by approximately threefold. 25 Because renal sympathetic tone is known to be enhanced in SHR, [26][27][28][29][30][31][32] it seems likely that this is the mechanism. In support of this hypothesis, regulation of BSC-1 by the sympathetic system is implicated by studies using an animal model of liver cirrhosis (chronic bile duct ligation), which show that renal denervation attenuates the sodium retention in such rats and is associated with normalization of the natriuretic effect of furosemide, as well as a significant reduction in the expression of BSC-1, suggesting an important role for renal sympathetic nerve activation in BSC-1 regulation.…”

Section: Discussionmentioning

confidence: 99%

CELLULAR DISTRIBUTION OF THE RENAL BUMETANIDE‐SENSITIVE Na–K–2Cl COTRANSPORTER BSC‐1 IN THE INNER STRIPE OF THE OUTER MEDULLA DURING THE DEVELOPMENT OF HYPERTENSION IN THE SPONTANEOUSLY HYPERTENSIVE RAT

Sonalker

Tofovic

Jackson

2007

Clin Exp Pharma Physio

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1. The renal bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1) is expressed only in the thick ascending limb and selectively traffics from intracellular vesicles (IVs) to apical plasma membranes (PMs), where BSC-1 regulates sodium reabsorption. We showed previously that in kidneys from adult spontaneously hypertensive rats (SHR; model of essential hypertension) total protein expression of BSC-1 was higher compared with kidneys from normotensive Wistar-Kyoto (WKY) rats. However, whether this change is associated with an increased trafficking of BSC-1 from IVs to PMs is unknown. The goal of the present study was to test the hypothesis that the increase in total renal BSC-1 protein expression in SHR is accompanied by an augmented distribution of BSC-1 from IVs to PMs. 2. To test the hypothesis, we obtained renal tissue from the inner stripe of the outer medulla (ISOM; enriched in thick ascending limbs) and isolated IVs and PMs from this tissue by differential centrifugation. Total BSC-1 protein expression in ISOM and BSC-1 protein expression in ISOM IVs and PMs were measured by semiquantitative western blotting in SHR and aged-matched WKY rats at different ages and stages of hypertension. 3. At 5 weeks of age, SHR were prehypertensive (mean arterial blood pressure (MABP) 97 mmHg). At this age, both the total abundance and cellular distribution of BSC-1 were similar in ISOM from SHR and WKY rats. 4. As SHR aged, their hypertension progressed (MABP 137 and 195 mmHg at 8 and 14 weeks of age, respectively). Associated with the increase in MABP was an increase in both steady state protein levels of ISOM BSC-1 and the distribution of ISOM BSC-1 to PMs (four- and sixfold increases at 8 and 14 weeks of age, respectively, compared with age-matched WKY rats; P < 0.001). 5. Using semiquantitative reverse transcription-polymerase chain reaction, BSC-1 mRNA was measured and was found not to differ between SHR and WKY rat ISOM at any age or level of MABP. 6. We conclude that as SHR transition from prehypertensive to established hypertension, there is a marked increase in the total expression of BSC-1 in ISOM that is not related to increases in steady state levels of BSC-1 mRNA and therefore unlikely to be due to changes in either the rate of BSC-1 gene transcription or the stability of BSC-1 mRNA. This suggests changes in either translational efficiency or BSC-1 protein stability in SHR. 7. We also conclude that the age/hypertension-related increase in BSC-1 protein levels in ISOM is accompanied by an equally marked increased trafficking of BSC-1 to PMs in SHR ISOM.

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Angiotensin II Receptor Modulation of Renal Vascular Resistance and Neurotransmission in Young and Adult Spontaneously Hypertensive Rats

Cited by 13 publications

References 29 publications

Hemodynamic, Morphometric and Autonomic Patterns in Hypertensive Rats - Renin-Angiotensin System Modulation

Hemodynamic, Morphometric and Autonomic Patterns in Hypertensive Rats - Renin-Angiotensin System Modulation

Endothelial nitric oxide synthase is predominantly involved in angiotensin II modulation of renal vascular resistance and norepinephrine release

CELLULAR DISTRIBUTION OF THE RENAL BUMETANIDE‐SENSITIVE Na–K–2Cl COTRANSPORTER BSC‐1 IN THE INNER STRIPE OF THE OUTER MEDULLA DURING THE DEVELOPMENT OF HYPERTENSION IN THE SPONTANEOUSLY HYPERTENSIVE RAT

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