Production of angiotensins I and II at tissue sites in intact pigs

Danser, A.H. Jan; Koning, M. M. G.; Admiraal, P. J. J.; Sassen, L. M. A.; Derkx, F. H. M.; Verdouw, Pieter D.; Schalekamp, M. A. D. H.

doi:10.1152/ajpheart.1992.263.2.h429

Cited by 57 publications

(56 citation statements)

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“…Plasma Ang I and II in untreated pigs were within the normal range. 19 No significant differences were observed between aortic and coronary venous plasma.…”

Section: Endogenous Angiotensins In Cardiac Tissue and Plasmamentioning

confidence: 89%

Angiotensin Production by the Heart

et al. 1998

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Background —Beneficial effects of ACE inhibitors on the heart may be mediated by decreased cardiac angiotensin II (Ang II) production. Methods and Results —To determine whether cardiac Ang I and Ang II are produced in situ or derived from the circulation, we infused 125 I-labeled Ang I or II into pigs (25 to 30 kg) and measured 125 I-Ang I and II as well as endogenous Ang I and II in cardiac tissue and blood plasma. In untreated pigs, the tissue Ang II concentration (per gram wet weight) in different parts of the heart was 5 times the concentration (per milliliter) in plasma, and the tissue Ang I concentration was 75% of the plasma Ang I concentration. Tissue 125 I-Ang II during 125 I-Ang II infusion was 75% of 125 I-Ang II in arterial plasma, whereas tissue 125 I-Ang I during 125 I-Ang I infusion was <4% of 125 I-Ang I in arterial plasma. After treatment with the ACE inhibitor captopril (25 mg twice daily), Ang II fell in plasma but not in tissue, and Ang I and renin rose both in plasma and tissue, whereas angiotensinogen did not change in plasma and fell in tissue. Tissue 125 I-Ang II derived by conversion from arterially delivered 125 I-Ang I fell from 23% to <2% of 125 I-Ang I in arterial plasma. Conclusions —Most of the cardiac Ang II appears to be produced at tissue sites by conversion of in situ–synthesized rather than blood-derived Ang I. Our study also indicates that under certain experimental conditions, the heart can maintain its Ang II production, whereas the production of circulating Ang II is effectively suppressed.

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“…Plasma Ang I and II in untreated pigs were within the normal range. 19 No significant differences were observed between aortic and coronary venous plasma.…”

Section: Endogenous Angiotensins In Cardiac Tissue and Plasmamentioning

confidence: 89%

Angiotensin Production by the Heart

et al. 1998

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“…D, Cell density in the neointima was significantly higher in the BB F2 rats than in the LL F2 rats, whereas no differences were observed in the media. pulmonary vascular bed is well known to be the primary site for the "in vivo" conversion of plasma angiotensin I, 54,55 and it has been suggested that the majority of plasma ACE is released by the pulmonary ECs. 49 On the other hand, there are no significant differences in the plasma renin activity and the plasma angiotensinogen, angiotensin I, and angiotensin II concentrations between the two strains.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin I-Converting Enzyme Genotype Influences Arterial Response to Injury in Normotensive Rats

Challah

Villard

Philippe

et al. 1998

ATVB

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Abstract-Two normotensive strains of rat, the Lou and Brown Norway (BN) strains, have contrasting levels of plasma angiotensin-converting enzyme (ACE). To investigate the degree of genetic determination of ACE expression, a polymorphic marker of the ACE gene was analyzed in inbred rats of the two strains. The two inbred strains were shown to bear different alleles for a polymorphic marker at the ACE gene. The segregation of the alleles of this marker and the plasma ACE levels were studied in a group of F2 rats issued from a cross between Lou and BN rats. The degree of genetic determination of plasma ACE activity was estimated to be 94% in the F2 cohort. The ACE locus accounts for 74% of total plasma ACE variance. ACE activity and mRNA expression in lungs were also genetically determined. The difference observed in ACE mRNA accumulation in the lungs between the two strains was due to a difference in the transcriptional rate of the ACE gene, as shown in nuclear run-on experiments. No differences were observed in arterial blood pressure of homozygous F2 progeny. In these animals, ACE genotype did not interfere with the pressor or the depressor responses to ACE-dependent vasoactive peptides. There was a significant effect of strain on constitutive or inducible membrane or soluble ACE activity in primary cultures of vascular cells. Neointima formation in the carotid artery 14 days after balloon injury was also influenced by the genotype in F2 homozygous progeny, whereas the medial area was not. These results demonstrate that there is a close relationship between the genetically determined ACE expression and the inducibility of the ACE gene. The degree of genetic determination of ACE expression in inbred rat strains offers a unique opportunity to study the interaction between genetic and environmental determinants of ACE expression and its involvement in response to experimental cardiovascular and renal injury. (Arterioscler Thromb Vasc Biol. 1998;18:235-243.)

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“…After an initial 30-minute period of baseline perfusion, perfusate for measurement of peptides was collected after 3,6,9,12,15,20,25,30,35,40, and 45 minutes. All perfusate samples were collected over a period of 9 seconds in the presence of a cocktail containing 26 mmol/L phenanthroline (Sigma Chemie), 125 mmol/L EDTA (Sigma Chemie), and a human specific renin inhibitor (remikiren, Hoffmann-La Roche) (10 Ϫ5 mol/L) to prevent any Ang formation outside the hindlimb.…”

Section: Hindlimb Perfusionmentioning

confidence: 99%

“…In fact, the tissues are the major site of Ang I and Ang II formation, and the release of locally formed Ang II contributes to the circulating levels of these peptides. [1][2][3] Kidney-derived renin is the major source of tissue renin. 4 Renin can be taken up by several tissues to react locally with its substrate angiotensinogen (Aogen).…”

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confidence: 99%

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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Production of angiotensins I and II at tissue sites in intact pigs

Cited by 57 publications

References 0 publications

Angiotensin Production by the Heart

Angiotensin Production by the Heart

Angiotensin I-Converting Enzyme Genotype Influences Arterial Response to Injury in Normotensive Rats

Effects of Human Prorenin in Rats Transgenic for Human Angiotensinogen

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