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M A Schalekamp - One of the best experts on this subject based on the ideXlab platform.

  • Angiotensin I-to-II conversion in the human renal vascular bed.
    Journal of Hypertension, 1998
    Co-Authors: A H Danser, P J Admiraal, F H Derkx, M A Schalekamp
    Abstract:

    Objective During previous studies in humans and pigs, using infusions of 125 I-angiotensin into the right antecubital vein or the left cardiac ventricle, we were unable to demonstrate conversion of arterial angiotensin I in the renal vascular bed. The arterial 125 I-angiotensin I levels in these studies may have been too low to result in detectable renal venous 125 I-angiotensin II levels, especially in view of the extensive degradation of angiotensins in the kidney. To overcome this problem, we now infused 125 I-angiotensin I directly into the renal artery. Design and Methods Five subjects (three women, two men) with essential hypertension (n = 4) or unilateral renal artery stenosis (n =1), not treated with an ACE inhibitor, were given a 10-min infusion of 125 I-angiotensin I (3.6 ± 0.4 x 10 6 cpm/min, mean ± SEM) into the left (n= 4) or right (n = 1) renal artery. Blood samples for the measurement of endogenous and radiolabelled angiotensin I and II were taken under steady-state conditions from the aorta and the renal vein of the 125 I-angiotensin I-perfused kidney. Results At steady-state, the levels of 125 I-angiotensin I in renal venous blood were 5-6 fold lower, and those of 125 I-angiotensin II were 4-5 fold higher than in renal arterial blood. On the basis of these levels, angiotensin I extraction in the renal vascular bed was calculated to be 80 ± 3%, of which 9 ± 1% was due to angiotensin I-to-II conversion. The renal venous levels of endogenous angiotensin I were 50% higher than its arterial levels, whereas the levels of endogenous angiotensin II were 50% lower in renal venous blood than in arterial blood. Taking into consideration the regional metabolism of arterially delivered angiotensins, and the generation of angiotensin I in circulating blood by plasma renin activity, it could be calculated that renal venous angiotensin I is largely derived from renal tissue sites, and that renal venous angiotensin II has no other sources than arterially delivered angiotensin I and II and angiotensin I generated by plasma renin activity in the renal vascular bed. Conclusions Less than 10 % of arterially delivered angiotensin I is converted to angiotensin II in the renal vascular bed. Conversion of angiotensin I generated at renal tissue sites does not contribute to the level of angiotensin II in the renal vein, although it is the main source of angiotensin II in renal tissue. Thus, the intrarenal formation of angiotensin II is highly compartmentalised.

  • Angiotensin I-to-II conversion in the human renal vascular bed.
    Journal of hypertension, 1998
    Co-Authors: A H Danser, P J Admiraal, F H Derkx, M A Schalekamp
    Abstract:

    During previous studies in humans and pigs, using infusions of 125I-angiotensin into the right antecubital vein or the left cardiac ventricle, we were unable to demonstrate conversion of arterial angiotensin I in the renal vascular bed. The arterial 125I-angiotensin I levels in these studies may have been too low to result in detectable renal venous 125I-angiotensin II levels, especially in view of the extensive degradation of angiotensins in the kidney. To overcome this problem, we now infused 125I-angiotensin I directly into the renal artery. Five subjects (three women, two men) with essential hypertension (n = 4) or unilateral renal artery stenosis (n = 1), not treated with an ACE inhibitor, were given a 10-min infusion of 125I-angiotensin I (3.6+/-0.4 x 10(6) cpm/min, mean +/- SEM) into the left (n = 4) or right (n = 1) renal artery. Blood samples for the measurement of endogenous and radiolabelled angiotensin I and II were taken under steady-state conditions from the aorta and the renal vein of the 125I-angiotensin I-perfused kidney. At steady-state, the levels of 125I-angiotensin I in renal venous blood were 5-6 fold lower, and those of 125I-angiotensin II were 4-5 fold higher than in renal arterial blood. On the basis of these levels, angiotensin I extraction in the renal vascular bed was calculated to be 80+/-3%, of which 9+/-1% was due to angiotensin I-to-II conversion. The renal venous levels of endogenous angiotensin I were 50% higher than its arterial levels, whereas the levels of endogenous angiotensin II were 50% lower in renal venous blood than in arterial blood. Taking into consideration the regional metabolism of arterially delivered angiotensins, and the generation of angiotensin I in circulating blood by plasma renin activity, it could be calculated that renal venous angiotensin I is largely derived from renal tissue sites, and that renal venous angiotensin II has no other sources than arterially delivered angiotensin I and II and angiotensin I generated by plasma renin activity in the renal vascular bed. Less than 10% of arterially delivered angiotensin I is converted to angiotensin II in the renal vascular bed. Conversion of angiotensin I generated at renal tissue sites does not contribute to the level of angiotensin II in the renal vein, although it is the main source of angiotensin II in renal tissue. Thus, the intrarenal formation of angiotensin II is highly compartmentalised.

Kenneth M. Baker - One of the best experts on this subject based on the ideXlab platform.

  • The intracellular Renin-Angiotensin system: implications in cardiovascular remodeling.
    Current opinion in nephrology and hypertension, 2008
    Co-Authors: Rajesh Kumar, Vivek Singh, Kenneth M. Baker
    Abstract:

    The Renin-Angiotensin system, traditionally viewed as a circulatory system, has significantly expanded in the last two decades to include independently regulated local systems in several tissues, newly identified active products of angiotensin II, and new receptors and functions of Renin-Angiotensin system components. In spite of our increased understanding of the Renin-Angiotensin system, a role of angiotensin II in cardiac hypertrophy, through direct effects on cardiovascular tissue, is still being debated. Here, we address the cardiovascular effects of angiotensin II and the role an intracellular Renin-Angiotensin system might play. Recent studies have shown that cardiac myocytes, fibroblasts and vascular smooth muscle cells synthesize angiotensin II intracellularly. Some conditions, such as high glucose, selectively increase intracellular generation and translocation of angiotensin II to the nucleus. Intracellular angiotensin II regulates the expression of angiotensinogen and renin, generating a feedback loop. The first reaction of intracellular angiotensin II synthesis is catalyzed by renin or cathepsin D, depending on the cell type, and chymase, not angiotensin-converting enzyme, catalyzes the second step. These studies suggest that the intracellular Renin-Angiotensin system is an important component of the local system. Alternative mechanisms of angiotensin II synthesis and action suggest a need for novel therapeutic agents to block the intracellular Renin-Angiotensin system.

  • The Cardiac Renin-Angiotensin System Conceptual, or a Regulator of Cardiac Function?
    Circulation research, 1999
    Co-Authors: David E. Dostal, Kenneth M. Baker
    Abstract:

    Angiotensin II, the effector peptide of the Renin-Angiotensin system, regulates cellular growth in response to developmental, physiological, and pathological processes. The identification of Renin-Angiotensin system components and angiotensin II receptors in cardiac tissue suggests the existence of an autocrine/paracrine system that has effects independent of angiotensin II derived from the circulatory system. To be functional, a local Renin-Angiotensin system should produce sufficient amounts of the autocrine and/or paracrine factor to elicit biological responses, contain the final effector (angiotensin II receptor), and respond to humoral, neural, and/or mechanical stimuli. In this review, we discuss evidence for a functional cardiac Renin-Angiotensin system.

A H Danser - One of the best experts on this subject based on the ideXlab platform.

  • Angiotensin I-to-II conversion in the human renal vascular bed.
    Journal of Hypertension, 1998
    Co-Authors: A H Danser, P J Admiraal, F H Derkx, M A Schalekamp
    Abstract:

    Objective During previous studies in humans and pigs, using infusions of 125 I-angiotensin into the right antecubital vein or the left cardiac ventricle, we were unable to demonstrate conversion of arterial angiotensin I in the renal vascular bed. The arterial 125 I-angiotensin I levels in these studies may have been too low to result in detectable renal venous 125 I-angiotensin II levels, especially in view of the extensive degradation of angiotensins in the kidney. To overcome this problem, we now infused 125 I-angiotensin I directly into the renal artery. Design and Methods Five subjects (three women, two men) with essential hypertension (n = 4) or unilateral renal artery stenosis (n =1), not treated with an ACE inhibitor, were given a 10-min infusion of 125 I-angiotensin I (3.6 ± 0.4 x 10 6 cpm/min, mean ± SEM) into the left (n= 4) or right (n = 1) renal artery. Blood samples for the measurement of endogenous and radiolabelled angiotensin I and II were taken under steady-state conditions from the aorta and the renal vein of the 125 I-angiotensin I-perfused kidney. Results At steady-state, the levels of 125 I-angiotensin I in renal venous blood were 5-6 fold lower, and those of 125 I-angiotensin II were 4-5 fold higher than in renal arterial blood. On the basis of these levels, angiotensin I extraction in the renal vascular bed was calculated to be 80 ± 3%, of which 9 ± 1% was due to angiotensin I-to-II conversion. The renal venous levels of endogenous angiotensin I were 50% higher than its arterial levels, whereas the levels of endogenous angiotensin II were 50% lower in renal venous blood than in arterial blood. Taking into consideration the regional metabolism of arterially delivered angiotensins, and the generation of angiotensin I in circulating blood by plasma renin activity, it could be calculated that renal venous angiotensin I is largely derived from renal tissue sites, and that renal venous angiotensin II has no other sources than arterially delivered angiotensin I and II and angiotensin I generated by plasma renin activity in the renal vascular bed. Conclusions Less than 10 % of arterially delivered angiotensin I is converted to angiotensin II in the renal vascular bed. Conversion of angiotensin I generated at renal tissue sites does not contribute to the level of angiotensin II in the renal vein, although it is the main source of angiotensin II in renal tissue. Thus, the intrarenal formation of angiotensin II is highly compartmentalised.

  • Angiotensin I-to-II conversion in the human renal vascular bed.
    Journal of hypertension, 1998
    Co-Authors: A H Danser, P J Admiraal, F H Derkx, M A Schalekamp
    Abstract:

    During previous studies in humans and pigs, using infusions of 125I-angiotensin into the right antecubital vein or the left cardiac ventricle, we were unable to demonstrate conversion of arterial angiotensin I in the renal vascular bed. The arterial 125I-angiotensin I levels in these studies may have been too low to result in detectable renal venous 125I-angiotensin II levels, especially in view of the extensive degradation of angiotensins in the kidney. To overcome this problem, we now infused 125I-angiotensin I directly into the renal artery. Five subjects (three women, two men) with essential hypertension (n = 4) or unilateral renal artery stenosis (n = 1), not treated with an ACE inhibitor, were given a 10-min infusion of 125I-angiotensin I (3.6+/-0.4 x 10(6) cpm/min, mean +/- SEM) into the left (n = 4) or right (n = 1) renal artery. Blood samples for the measurement of endogenous and radiolabelled angiotensin I and II were taken under steady-state conditions from the aorta and the renal vein of the 125I-angiotensin I-perfused kidney. At steady-state, the levels of 125I-angiotensin I in renal venous blood were 5-6 fold lower, and those of 125I-angiotensin II were 4-5 fold higher than in renal arterial blood. On the basis of these levels, angiotensin I extraction in the renal vascular bed was calculated to be 80+/-3%, of which 9+/-1% was due to angiotensin I-to-II conversion. The renal venous levels of endogenous angiotensin I were 50% higher than its arterial levels, whereas the levels of endogenous angiotensin II were 50% lower in renal venous blood than in arterial blood. Taking into consideration the regional metabolism of arterially delivered angiotensins, and the generation of angiotensin I in circulating blood by plasma renin activity, it could be calculated that renal venous angiotensin I is largely derived from renal tissue sites, and that renal venous angiotensin II has no other sources than arterially delivered angiotensin I and II and angiotensin I generated by plasma renin activity in the renal vascular bed. Less than 10% of arterially delivered angiotensin I is converted to angiotensin II in the renal vascular bed. Conversion of angiotensin I generated at renal tissue sites does not contribute to the level of angiotensin II in the renal vein, although it is the main source of angiotensin II in renal tissue. Thus, the intrarenal formation of angiotensin II is highly compartmentalised.

Kong I. Lie - One of the best experts on this subject based on the ideXlab platform.

  • Activated tissue Renin-Angiotensin systems add to the progression of heart failure
    Basic Research in Cardiology, 1996
    Co-Authors: Ym Pinto, Hendrik Buikema, Van Wiekert Gilst, Kong I. Lie
    Abstract:

    In this paper, we review the hypothesis that activated tissue Renin-Angiotensin systems play a detrimental role in heart failure. The main arguments for this idea are discussed: a) tissue Renin-Angiotensin systems behave functionally distinct from the circulating Renin-Angiotensin system; b) tissue Renin-Angiotensin systems are activated in heart failure; c) activated tissue Renin-Angiotensin systems induce cardiovascular dysfunction.

  • Activated tissue Renin-Angiotensin systems add to the progression of heart failure.
    Basic research in cardiology, 1996
    Co-Authors: Ym Pinto, Hendrik Buikema, W H Van Gilst, Kong I. Lie
    Abstract:

    In this paper, we review the hypothesis that activated tissue Renin-Angiotensin systems play a detrimental role in heart failure. The main arguments for this idea are discussed: a) tissue Renin-Angiotensin systems behave functionally distinct from the circulating Renin-Angiotensin system; b) tissue Renin-Angiotensin systems are activated in heart failure; c) activated tissue Renin-Angiotensin systems induce cardiovascular dysfunction. Finally, this hypothesis predicts that optimal treatment in heart failure requires the inhibition of tissue Renin-Angiotensin systems. However, studies pertaining to this prediction are still lacking, particularly in human subjects.

Ym Pinto - One of the best experts on this subject based on the ideXlab platform.

  • Activated tissue Renin-Angiotensin systems add to the progression of heart failure
    Basic Research in Cardiology, 1996
    Co-Authors: Ym Pinto, Hendrik Buikema, Van Wiekert Gilst, Kong I. Lie
    Abstract:

    In this paper, we review the hypothesis that activated tissue Renin-Angiotensin systems play a detrimental role in heart failure. The main arguments for this idea are discussed: a) tissue Renin-Angiotensin systems behave functionally distinct from the circulating Renin-Angiotensin system; b) tissue Renin-Angiotensin systems are activated in heart failure; c) activated tissue Renin-Angiotensin systems induce cardiovascular dysfunction.

  • Activated tissue Renin-Angiotensin systems add to the progression of heart failure.
    Basic research in cardiology, 1996
    Co-Authors: Ym Pinto, Hendrik Buikema, W H Van Gilst, Kong I. Lie
    Abstract:

    In this paper, we review the hypothesis that activated tissue Renin-Angiotensin systems play a detrimental role in heart failure. The main arguments for this idea are discussed: a) tissue Renin-Angiotensin systems behave functionally distinct from the circulating Renin-Angiotensin system; b) tissue Renin-Angiotensin systems are activated in heart failure; c) activated tissue Renin-Angiotensin systems induce cardiovascular dysfunction. Finally, this hypothesis predicts that optimal treatment in heart failure requires the inhibition of tissue Renin-Angiotensin systems. However, studies pertaining to this prediction are still lacking, particularly in human subjects.

  • HYPERACTIVE TISSUE Renin-Angiotensin SYSTEMS IN CARDIOVASCULAR DYSFUNCTION - EXPERIMENTAL-EVIDENCE AND CLINICAL HYPOTHESES
    Clinical and experimental hypertension (New York N.Y. : 1993), 1995
    Co-Authors: Ym Pinto, Hendrik Buikema, Van Wiekert Gilst
    Abstract:

    In this review, hypotheses are discussed with regard to the role of local, tissue Renin-Angiotensin systems in the progression of cardiovascular dysfunction. After local Renin-Angiotensin systems had been described as functionally distinct systems, recent experimental studies have suggested an association between hyperactivity of these local Renin-Angiotensin systems, and cardiovascular dysfunction. Moreover, the existence of these local renin- angiotensin systems has been confirmed in humans, and early data indicate that the human cardiac Renin-Angiotensin system may be activated in heart disease. Furthermore, polymorphisms in genes coding for the Renin-Angiotensin system seem associated with hypertension and left ventricular hypertrophy. These observations may be clinically relevant as inhibition of local Renin-Angiotensin systems may be an important prerequisite to obtain an optimal clinical effect.