If you are experiencing problems downloading PDF or HTML fulltext, our helpdesk recommend clearing your browser cache and trying again. If you need help in clearing your cache, please click here . Still need help? Email help@ingentaconnect.com

Renal medullary effects of transient prehypertensive treatment in young spontaneously hypertensive rats

$48.00 plus tax (Refund Policy)

Download / Buy Article:

Abstract:

Abstract Aim: 

Transient angiotensin II receptor blockade (ARB) leads to prolonged blood pressure (BP) lowering, but the underlying mechanism remains uncertain. Long-term BP control is regulated by the medullary microcirculation with the pericyte as contractile cell. We hypothesize that the prolonged BP effect is caused by increased medullary blood flow (MBF) associated with structural alterations based on reduced medullary pericyte number. Methods: 

Four-week-old spontaneously hypertensive rats (SHR) were treated for 4 weeks with losartan (SHR-Los: 20 mg kg−1 day−1), hydralazine (SHR-Hyd: 15 mg kg−1 day−1), losartan and pan-caspase inhibitor zVAD (SHR-Los + 1 mg kg−1 day−1 zVAD), losartan and glycogen synthase kinase-3β (GSK) inhibitor valproate (SHR-Los + 10 mg kg−1 day−1 Val) or placebo. BP, MBF and pericyte number were determined under and after treatment (8 and 12 weeks). Apoptotic pericytes were determined with α-actin and TUNEL double staining. Sodium concentration was determined in renal medulla and urine. Results: 

Antihypertensive treatment equipotently reduced BP at 8 weeks of age. After drug withdrawal (12 weeks of age) BP reduction was restricted to SHR-Los (SHR-Los: 153 ± 5, SHR-Hyd: 177 ± 2, SHR: 184 ± 3 mmHg). Simultaneously, MBF was increased and pericyte number reduced, while medullary and urinary sodium concentration increased. Transient ARB in combination with zVAD or valproate resulted in more medullary pericytes and higher BP (SHR-Los/zVAD: 164 ± 7; SHR-Los/Val: 168 ± 6 mmHg) compared with transient ARB alone. Conclusion: 

After drug withdrawal, transient ARB leads to increased MBF and is associated with a reduction in medullary pericytes. This may be associated with pericyte apoptosis as anti-apoptosis during transient ARB increases pericyte number and BP.

Keywords: developmental window of hypertension; medullary blood flow; pericyte; renal medulla

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1748-1716.2008.01916.x

Affiliations:  Department of Pharmacology & Toxicology, CARIM, University Maastricht, Maastricht, the Netherlands

Publication date: June 1, 2009

Related content

Tools

Favourites

Share Content

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
ingentaconnect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more