Localization and Production of Angiotensin II in the Isolated Perfused Rat Heart

Lannoy, Larissa M. de; Danser, A.H. Jan; Bouhuizen, Angelique M.; Saxena, Pramod R.; Schalekamp, M. A. D. H.

doi:10.1161/01.hyp.31.5.1111

Cited by 77 publications

(44 citation statements)

References 37 publications

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“…However, we and others have obtained similar results for local Ang formation with different renin sources in the rat model. 6,[27][28][29] Recently, Hu et al 30 showed identical hemodynamic and hormonal responses to 14-day infusions of renin or Ang II in conscious rats. They concluded that tissue-bound renin does not play a unique role in promoting cardiovascular, renal, hormonal, or drinking responses.…”

Section: Discussionmentioning

confidence: 96%

Effects of Human Prorenin in Rats Transgenic for Human Angiotensinogen

Müller

Hilgers²,

Mathews³

et al. 1999

Hypertension

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Abstract-The physiological role of prorenin is unknown; however, the possibility that prorenin inhibits renin locally has been suggested. We tested the hypothesis that prorenin may be an endogenous competitor for renin uptake in the tissue. We also investigated whether prorenin can be activated to active renin and affect mean arterial pressure (MAP). Isolated perfused hindquarters of rats transgenic for human angiotensinogen were infused with human renin and/or prorenin. The plateau phase of angiotensin (Ang) I release 15 minutes after cessation of infusions was used as a parameter for renin uptake. Renin (10 ng/mL for 15 minutes) caused sustained release of Ang I (153Ϯ16 fmol/mL). Coinfusion with a 15-fold excess of prorenin did not affect local Ang I formation (153Ϯ19 fmol/mL). Prorenin infusion alone showed no activation to active renin. In addition, we investigated MAP and plasma Ang II levels after injection of saline (⌬MAP, Ϫ1Ϯ2 mm Hg; 40Ϯ5 fmol/mL Ang II), 9 ng renin (⌬MAP, ϩ37Ϯ3 mm Hg; 378Ϯ39 fmol/mL), and 144 ng prorenin (⌬MAP, ϩ10Ϯ5 mm Hg; 61Ϯ5 fmol/mL) and the coinjection of renin and prorenin (⌬MAP, ϩ41Ϯ4 mm Hg; 305Ϯ23 fmol/mL) in anesthetized rats. The data show that prorenin was not activated to active renin and did not affect MAP in short-term experiments. Renin-induced Ang formation was not affected by prorenin. Renin may have been taken up specifically because of its physical and chemical properties or because of nonspecific sequestration in the extravascular space. We conclude that prorenin does not act as an endogenous antagonist for the long-lasting effects of renin in the vascular wall. Moreover, prorenin does not affect acute renin-related effects on blood pressure.

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Section: Discussionmentioning

confidence: 96%

Effects of Human Prorenin in Rats Transgenic for Human Angiotensinogen

Müller

Hilgers²,

Mathews³

et al. 1999

Hypertension

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“…Alternatively and perhaps more likely in view of the rapid activation process, cell-activated prorenin may contribute to intracellular angiotensin generation before its destruction. Several studies have provided evidence for intracellular angiotensin generation (17,32,42), and ANG II is known to activate intracellular AT 1 receptors in the cytosol and nucleus (23,27). In the absence of local renin synthesis, such intracellular angiotensin generation will depend on the uptake of circulating renin or prorenin.…”

Section: Discussionmentioning

confidence: 99%

High-affinity prorenin binding to cardiac man-6-P/IGF-II receptors precedes proteolytic activation to renin

Saris¹,

Derkx²,

Bruin³

et al. 2001

American Journal of Physiology-Heart and Circulatory Physiology

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105

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“…22 Local angiotensin formation in the heart may contribute to the pathogenesis of cardiac hypertrophy, congestive heart failure, and tissue remodeling. 23 We have reported that rat and human blood vessels produce aldosterone.…”

Section: Discussionmentioning

confidence: 99%

Cardiac Aldosterone Production in Genetically Hypertensive Rats

et al. 2000

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Abstract-Aldosterone is synthesized in extra-adrenal tissues, both blood vessels and brain. We undertook the present study to determine whether the rat heart produces aldosterone and to investigate the effects of adrenalectomy, ACE inhibition, and angiotensin II on aldosterone synthesis in the heart. To clarify the pathophysiological role of cardiac aldosterone in the hypertensive heart, we compared the synthesis of aldosterone in the hearts of stroke-prone spontaneously hypertensive rats (SHRSP) with that in Wistar-Kyoto rats. The effects of the aldosterone antagonist spironolactone on myocardial hypertrophy in adrenalectomized SHRSP were also studied. Isolated rat hearts were perfused for 2 hours, and the perfusate was analyzed with HPLC and mass spectrometry. The activity of aldosterone synthase was estimated on the basis of the conversion of [ 14 C]deoxycorticosterone to [ 14 C]aldosterone. The levels of aldosterone synthase gene (CYP11B2) mRNA were determined with competitive polymerase chain reaction. Aldosterone production, the activity of aldosterone synthase, and the expression of CYP11B2 mRNA were increased in hearts from adrenalectomized rats and rats treated with angiotensin II. ACE inhibitors decreased cardiac aldosterone synthesis. Cardiac aldosterone, aldosterone synthase activity, and CYP11B2 mRNA levels in hearts from 2-and 4-week-old SHRSP were significantly greater than those of age-matched Wistar-Kyoto rats. Spironolactone prevented cardiac hypertrophy in adrenalectomized SHRSP. These results suggest that the rat heart produces aldosterone and that endogenous cardiac aldosterone may affect cardiac function and hypertrophy in hypertension in rats. (Hypertension. 2000;36:495-500.)Key Words: heart Ⅲ rats, inbred strains Ⅲ aldosterone Ⅲ hypertrophy Ⅲ cytochrome p450 Ⅲ mRNA A ldosterone receptors are present in cardiac myocytes, endocardial endothelial cells, and cardiac fibroblasts. 1 The peripheral infusion of aldosterone in rats causes cardiac hypertrophy and cardiac fibrosis without increasing the blood pressure. 2 In cultured neonatal rat fibroblasts or cardiomyocytes, aldosterone increases collagen synthesis and protein synthesis. 3,4 Physiologically significant amounts of mineralocorticoids are believed to be synthesized only in the adrenal cortex. However, extra-adrenal steroid 21-hydroxylation and 11␤-hydroxylation occur in a variety of human tissues. Circulating progesterone is converted to deoxycorticosterone (DOC) and DOC sulfate in adult and fetal human extra-adrenal tissues. 5 The extra-adrenal expression of steroid 21-hydroxylase and 11␤-hydroxylase by a benign testicular Leydig cell tumor has also been reported. 6 We reported that aldosterone, synthesized in the vasculature, is in part controlled by angiotensin (Ang) II and participates in the development of vascular hypertrophy that correlates with Ang II concentration. 7,8 We performed the present study to determine whether the rat heart produces aldosterone and to investigate the effects of adrenalectomy, ACE inhibitor, and Ang ...

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Localization and Production of Angiotensin II in the Isolated Perfused Rat Heart

Cited by 77 publications

References 37 publications

Effects of Human Prorenin in Rats Transgenic for Human Angiotensinogen

Effects of Human Prorenin in Rats Transgenic for Human Angiotensinogen

High-affinity prorenin binding to cardiac man-6-P/IGF-II receptors precedes proteolytic activation to renin

Cardiac Aldosterone Production in Genetically Hypertensive Rats

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