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

Baumann, Marcus; Janssen, Ben J. A.; Hermans, J.; Bartholomé, Roger; Smits, J. F. M.; Struijker‐Boudier, Harry A.J.

doi:10.1111/j.1748-1716.2008.01916.x

Cited by 16 publications

(16 citation statements)

References 28 publications

(35 reference statements)

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“…[10,11]. We previously localized the role of the RAS, particularly, in the renal medullary microcirculation [11]. Renal medullary pericytes are increased in number in young SHR and they are able to contract vasa recta.…”

Section: Discussionmentioning

confidence: 98%

“…Renal medullary pericytes are increased in number in young SHR and they are able to contract vasa recta. TPT with RAS blockers leads to a reduction in the number of pericytes and, thus, enhances renal medullary blood flow [10,11]. The attenuation of decreased renal medullary blood flow may contribute to the protection against Ang II-induced structural damage to the kidney.…”

Section: Discussionmentioning

confidence: 98%

“…I3C, indole-3-carbinol; PAS-D, periodic acid-Schiff diastase. [10,11]. We previously localized the role of the RAS, particularly, in the renal medullary microcirculation [11].…”

Section: Discussionmentioning

confidence: 98%

“…Recent studies suggest that the long-lasting attenuation of hypertension following transient prehypertensive treatment (TPT) of SHR with RAS inhibitors is due to an intrarenal action of these drugs. Particularly, structural alterations in the renal microcirculation determine the long-lasting antihypertensive effects of RAS inhibitors following TPT [10,11]. The critical period of effective TPT of SHR with RAS inhibitors is between 4 and 8 weeks postnatally.…”

Section: Introductionmentioning

confidence: 99%

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Transient renin–angiotensin system stimulation in an early stage of life causes sustained hypertension in rats

Heijnen

Peutz‐Kootstra²,

Mullins³

et al. 2011

Journal of Hypertension

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

“…I3C, indole-3-carbinol; PAS-D, periodic acid-Schiff diastase. [10,11]. We previously localized the role of the RAS, particularly, in the renal medullary microcirculation [11].…”

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Transient renin–angiotensin system stimulation in an early stage of life causes sustained hypertension in rats

Heijnen

Peutz‐Kootstra²,

Mullins³

et al. 2011

Journal of Hypertension

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“…Several authors suggested that reduced angiotensin sensitivity is involved in the long-lasting cardiovascular protection (Bergström et al, 2002;Baumann et al, 2009). Angiotensin signaling is related to the expression level of the AT1R, but it is also regulated by its internalization which is controlled by the (AT1R)-associated protein (ATRAP).…”

mentioning

confidence: 99%

Prehypertensive Preconditioning Improves Adult Antihypertensive and Cardioprotective Treatment

Baumann¹,

Sollinger²,

Roos³

et al. 2009

J Pharmacol Exp Ther

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Transient prehypertensive treatment (TPT) causes prolonged antihypertensive and cardioprotective effects. Reduced angiotensin sensitivity has been attributed to those effects. We hypothesize that prehypertensive preconditioning by angiotensin II type 1 receptor (AT1R) blockade improves cardiovascular protection of late-onset AT1R blockade in a model of spontaneous hypertensive heart-failure rats (SHHF/Mcc-fa cp ). TPT (4 -8 weeks of age) consisted of AT1R blockade (5 mg/kg candesartan) or vehicle. Candesartan-pretreated SHHF (5 mg/ kg/day candesartan; weeks 4 -8) received during adulthood (20 -28 weeks of age) either candesartan at a dose of 1.5 or 5 mg/kg/day or vehicle. Vehicle-pretreated SHHF received either candesartan (5 mg/kg/day) or vehicle during adulthood. Blood pressure telemetry and longitudinal echocardiography were performed between weeks 20 and 28. Final examination included cardiac and vascular morphometry and measurement of the AT1R signaling and receptor internalization (ATRAP). Combined juvenile and adult AT1R blockade caused lower mean arterial pressure (MAP) than adult AT1R blockade alone (84 Ϯ 5 versus 97 Ϯ 5 mm Hg; P Ͻ 0.05). Cardiac and vascular hypertrophy was lower. Juvenile treatments were associated with a reduced cardiovascular AT1R expression and enhanced ATRAP expression. Combined juvenile and reduced adult AT1R blockade resulted in MAP similar to that with adult AT1R blockade alone (92 Ϯ 3 versus 97 Ϯ 5 mm Hg). We conclude that prehypertensive preconditioning improves adult treatment effects in SHHF. Those effects correlate with reduced cardiovascular AT1R expression and enhanced receptor internalization, suggesting reduced angiotensin sensitivity in pretreated SHHF. Moreover, preconditioning allows a reduction of adult AT1R blockade without loss of protection. Therefore, prehypertensive preconditioning may offer a tool to improve treatment efficacy in humans.The awareness of hypertension is poor and, consequently, so is appropriate antihypertensive treatment (Cutler et al., 2008). Therefore, alternative treatment strategies for hypertension and cardiovascular complications are of particular interest. The trial of preventing hypertension (TROPHY) was the first clinical study to demonstrate that a transient prehypertensive treatment (TPT) could successfully delay new onset of hypertension in a cohort of prehypertensive subjects 2 years after withdrawal of an angiotensin II type 1 receptor (AT1R) blocker compared with placebo (Julius et al., 2006). However, TROPHY raised the concern that TPT was a promotion for earlier use of antihypertensive drugs rather than a reliable and efficient addition to antihypertensive treatment (AHT) (Baumann and van den Born, 2006;Grassi, 2006;Meltzer, 2006;Persell and Baker, 2006;Nesbitt, 2007). Indeed, this context has not been investigated in detail. Thus, it remains unclear whether TPT is as effective in blood pressure-lowering and end-organ protection as continuous AHT starting at adulthood. Up to now, the potential preconditioning effects o...

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Necroptosis mediated by receptor interaction protein kinase 1 and 3 aggravates chronic kidney injury of subtotal nephrectomised rats

Zhu

Cui

Gan

et al. 2015

Biochemical and Biophysical Research Communications

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

Abstract: 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.

Cited by 16 publications

References 28 publications

Transient renin–angiotensin system stimulation in an early stage of life causes sustained hypertension in rats

Transient renin–angiotensin system stimulation in an early stage of life causes sustained hypertension in rats

Prehypertensive Preconditioning Improves Adult Antihypertensive and Cardioprotective Treatment

Necroptosis mediated by receptor interaction protein kinase 1 and 3 aggravates chronic kidney injury of subtotal nephrectomised rats

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