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Angiotensin II in hypertension, renal damage and renal vascular function
Institutt for Indremedisin, Universitetet i Bergen. (Renal Research Group)
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Bergen: Universitetet i Bergen, 2010.
National Category
Physiology
Identifiers
URN: urn:nbn:se:uu:diva-177054ISBN: 9788230815670 (print)OAI: oai:DiVA.org:uu-177054DiVA: diva2:538972
Public defence
2010-08-27, Bergen, 10:00 (English)
Opponent
Supervisors
Available from: 2012-07-09 Created: 2012-07-02 Last updated: 2017-02-01Bibliographically approved
List of papers
1. AT(1) receptor activation regulates the mRNA expression of CAT1, CAT2, arginase-1, and DDAH2 in preglomerular vessels from angiotensin II hypertensive rats.
Open this publication in new window or tab >>AT(1) receptor activation regulates the mRNA expression of CAT1, CAT2, arginase-1, and DDAH2 in preglomerular vessels from angiotensin II hypertensive rats.
2009 (English)In: American Journal of Physiology - Renal Physiology, ISSN 0363-6127, E-ISSN 1522-1466, Vol. 297, no 1, F163-8 p.Article in journal (Refereed) Published
Abstract [en]

Previously, we found increased expression of l-arginine metabolizing enzymes in both kidneys from two-kidney, one-clip (2K1C) hypertensive rats (Helle F, Hultstrom M, Skogstrand T, Palm F, Iversen BM. Am J Physiol Renal Physiol 296: F78-F86, 2009). In the present study, we investigate whether AT(1) receptor activation can induce the changes observed in 2K1C. Four groups of rats were infused with 80 ng/min ANG II or saline for 14 days and/or given 60 mg x kg(-1) x day(-1) losartan. Gene expression was studied in isolated preglomerular vessels by RT-PCR. Dose-responses to ANG II were studied in isolated preglomerular vessels with and without acute NOS inhibition [10(-4) mol/l N(G)-nitro-l-arginine methyl ester (l-NAME)]. Expressions of endothelial nitric oxide synthase (eNOS), caveolin-1, and arginase-2 were not changed by ANG II infusion. CAT1 (0.3 8 +/- 0.07 to 0.73 +/- 0.12, P < 0.05), CAT2 (1.14 +/- 0.29 to 2.74 +/- 0.48), DDAH2 (1.09 +/- 0.27 to 2.3 +/- 0.46), and arginase-1 (1.08 +/- 0.17 to 1.82 +/- 0.22) were increased in ANG II-infused rats. This was prevented by losartan treatment, which reduced the expression of eNOS (0.97 +/- 0.26 to 0.37 +/- 0.11 in controls; 0.8 +/- 0.16 to 0.36 +/- 0.1 in ANG II-infused rats) and caveolin-1 (2.49 +/- 0.59 to 0.82 +/- 0.24 in controls and 2.59 +/- 0.61 to 1.1 +/- 0.25 in ANG II-infused rats). ANG II (10(-10) mol/l) caused vessels from ANG II-infused animals to contract to 53 +/- 15% of baseline diameter and 90 +/- 5% of baseline diameter in controls (P < 0.05) and was further enhanced by l-NAME to 4 +/- 4% of baseline diameter (P < 0.05). In vivo losartan treatment reduced the reactivity of isolated vessels to 91 +/- 2% of baseline in response to 10(-7) mol/l ANG II compared with 82 +/- 3% in controls (P < 0.05) and prevented the increased responsiveness caused by ANG II infusion. In conclusion, CAT1, CAT2, DDAH2, and arginase-1 expression in renal resistance vessels is regulated through the AT(1) receptor. This finding may be of direct importance for NOS and the regulation of preglomerular vascular function.

National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-170523 (URN)10.1152/ajprenal.00087.2009 (DOI)19386725 (PubMedID)
Available from: 2012-07-02 Created: 2012-03-12 Last updated: 2017-12-07
2. Angiotensin II-induced contraction is attenuated by nitric oxide in afferent arterioles from the nonclipped kidney in 2K1C
Open this publication in new window or tab >>Angiotensin II-induced contraction is attenuated by nitric oxide in afferent arterioles from the nonclipped kidney in 2K1C
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2009 (English)In: American Journal of Physiology - Renal Physiology, ISSN 0363-6127, E-ISSN 1522-1466, Vol. 296, no 1, F78-F86 p.Article in journal (Refereed) Published
Abstract [en]

Two-kidney, one-clip (2K1C) is a model of renovascular hypertension where we previously found an exaggerated intracellular calcium (Ca(i)(2+)) response to ANG II in isolated afferent arterioles (AAs) from the clipped kidney (Helle F, Vagnes OB, Iversen BM. Am J Physiol Renal Physiol 291: F140-F147, 2006). To test whether nitric oxide (NO) ameliorates the exaggerated ANG II response in 2K1C, we studied ANG II (10(-7) mol/l)-induced calcium signaling and contractility with or without the NO synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME). In AAs from the nonclipped kidney, l-NAME increased the ANG II-induced Ca(i)(2+) response from 0.28 +/- 0.05 to 0.55 +/- 0.09 (fura 2, 340 nm/380 nm ratio) and increased contraction from 80 +/- 6 to 60 +/- 6% of baseline (P < 0.05). In vessels from sham and clipped kidneys, l-NAME had no effect. In diaminofluorescein-FM diacetate-loaded AAs from the nonclipped kidney, ANG II increased NO-derived fluorescence to 145 +/- 34% of baseline (P < 0.05 vs. sham), but not in vessels from the sham or clipped kidney. Endothelial NOS (eNOS) mRNA and ser-1177 phosphorylation were unchanged in both kidneys from 2K1C, while eNOS protein was reduced in the clipped kidney compared with sham. Cationic amino acid transferase-1 and 2 mRNAs were increased in 2K1C, indicating increased availability of l-arginine for NO synthesis, but counteracted by decreased scavenging of the eNOS inhibitor asymmetric dimethylarginine by dimethylarginine dimethylaminohydrolase 2. In conclusion, the Ca(i)(2+) and contractile responses to ANG II are blunted by NO release in the nonclipped kidney. This may protect the nonclipped kidney from the hypertension and elevated ANG II levels in 2K1C.

Keyword
two-kidney, one-clip, renovascular hypertension
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-102177 (URN)10.1152/ajprenal.90518.2008 (DOI)000262101200009 ()18945823 (PubMedID)
Available from: 2009-05-05 Created: 2009-05-05 Last updated: 2017-12-13
3. Prevention of hypertension and organ damage in 2-kidney, 1-clip rats by tetradecylthioacetic acid.
Open this publication in new window or tab >>Prevention of hypertension and organ damage in 2-kidney, 1-clip rats by tetradecylthioacetic acid.
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2006 (English)In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 48, no 3, 460-6 p.Article in journal (Refereed) Published
Abstract [en]

Dietary lipids are reported to affect the blood pressure in both humans and experimental animal models with hypertension. In the present study, 2-kidney, 1-clip (2K1C) hypertensive rats were treated with the modified fatty acid tetradecylthioacetic acid (TTA) from the time of clipping or after hypertension was established. TTA treatment attenuated the development of hypertension and reduced established 2K1C hypertension. The mRNA level of renin in the clipped kidney and the plasma renin activity were markedly reduced, and the plasma angiotensin II level tended to decrease after TTA treatment. In addition, TTA reduced the mRNA level of angiotensinogen in white adipose tissue. Prevention of organ damage was demonstrated by normal urinary excretion of protein, maintained serum albumin, lower heart weight, and clearly reduced vascular, glomerular, and tubulointerstitial damage in the nonclipped kidney. Renal function was not affected as estimated by unchanged plasma creatinine. Furthermore, the serum levels of triacylglycerol and cholesterol were reduced by TTA. The serum fatty acid composition was changed, resulting in a favorable increase of oleic acid. However, the levels of all of the omega-3 fatty acids and of linoleic acid were reduced, and no change was seen in the level of arachidonic acid, but the urinary excretion of 8-iso-prostaglandin F2alpha was declined. In conclusion, TTA attenuated the development of hypertension, reduced established hypertension, and prevented the development of organ damage in 2K1C rats, possibly by reducing the amounts of the vasoconstrictors angiotensin II and 8-iso-prostaglandin F2alpha and by inducing a favorable increase of oleic acid in serum.

National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-170526 (URN)10.1161/01.HYP.0000233018.60736.70 (DOI)16847149 (PubMedID)
Available from: 2012-07-02 Created: 2012-03-12 Last updated: 2017-12-07

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