Angiotensin converting enzyme activity and hypoxia

Milledge, J. S.; Catley, D. M.

doi:10.1042/cs0720149

Cited by 25 publications

(18 citation statements)

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“…A few years ago, Milledge & Catley (1984) suggested that although renin activity is increased in systemic hypoxia, ACE activity is inhibited, so allowing a marked disparity in the extent to which renin and AII levels are increased in different individuals: this was used to explain the differences between individuals in their susceptibility to acute mountain sickness. However, after performing further series of experiments, Milledge & Catley (1987) completely withdrew their claim that hypoxia inhibits ACE activity. Thus, it is reasonable to assume that raised AII levels had the potential to influence cardiovascular and renal function in hypoxia in the present study.…”

Section: Discussionmentioning

confidence: 99%

The role of the renin‐angiotensin system in the renal response to moderate hypoxia in the rat.

Neylon

Marshall

Johns

1996

The Journal of Physiology

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1. In two groups of Saffan-anaesthetized rats, we studied the role of the renin-angiotensin system in mediating the antidiuresis and antinatriuresis induced by moderate systemic hypoxia. 2. In both groups, a first period of hypoxia (breathing 12% 02 for 20 min) induced a fall in arterial partial pressure of 02 (Pa°2; to 42 mmHg), a fall in mean arterial pressure (MABP), no change in renal blood flow (RBF) due to an increase in renal vascular conductance (RVC = RBF/MABP) and falls in urine flow and absolute sodium excretion (UNa V). Concomitantly, plasma renin activity increased from 3-08 + 0-68 (mean + S.E.M.) to 8 36 + 18 ng ml-hrF. 3. In group 1 (n = 11), Losartan (10 mg kg-, i.v.), the angiotensin (AII) AT1 receptor antagonist, induced a fall in MABP (115 + 3 to 90 + 3 mmHg), an increase in RVC such that RBF was unchanged, and falls in glomerular filtration rate (GFR), urine flow and UNa V. However, hypoxia induced qualitatively similar changes to those seen before Losartan treatment. 4. In group 2 (n = 9), we occluded the aorta distal to the renal artery to prevent basal MABP and renal perfusion pressure (RPP) from falling after addition of Losartan and to keep the hypoxia-induced fall in MABP the same as before Losartan treatment. Nevertheless, Losartan induced an increase in basal RVC, RBF, urine flow and UNa V whilst hypoxia induced falls in urine flow and UN. V that were proportionately similar to those seen prior to addition of Losartan. 5. These results indicate that in the Saffan-anaesthetized rat, AII exerts tonic, renal vasoconstrictor and consequent antidiuretic and antinatriuretic influences in normoxia, but does not contribute to the hypoxia-induced antidiuresis and antinatriuresis. We propose that renin secretion is increased by the hypoxia-induced fall in RPP rather than by an increase in renal sympathetic activity. Thus, the AII generated cannot produce antidiuresis and antinatriuresis by its known facilitatory influence on the actions of an increase in sympathetic activity on the renal tubules and is insufficient to produce these effects by direct actions. Rather, these results support the view that the antidiuresis and antinatriuresis of moderate hypoxia is predominantly due to the fall in RPP.Some individuals who climb to high altitude show diuresis and natriuresis and tolerate the hypoxia well. Others show antidiuresis and antinatriuresis and commonly succumb to mountain sickness (Milledge & Catley, 1984;Honig, 1989). The antidiuresis and antinatriuresis has been attributed to the actions of angiotensin II (AII) upon the kidney, the AII being generated by hypoxia-induced stimulation of the renin-angiotensin system (Milledge & Catley, 1984.Although an increase in renin secretion might be explained as a reflex response to an increase in renal sympathetic activity caused by hypoxic stimulation of peripheral chemoreceptors (Marshall, 1994), this conclusion cannot be firmly drawn from high altitude studies, because those who climb to high altitude not only experience systemic hypoxia, but also ...

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Section: Discussionmentioning

confidence: 99%

The role of the renin‐angiotensin system in the renal response to moderate hypoxia in the rat.

Neylon

Marshall

Johns

1996

The Journal of Physiology

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“…In recent years, attention has shifted towards candidate genes, notable among them being the ACE gene (Rupert et al 1999 ;Morell et al 1999) and its insertion\ deletion (I\D) polymorphism in particular. This has been the primary choice because of the clinical importance of the enzyme in the regulation of blood pressure (BP), even at altitude (Milledge & Catley, 1987 ;Morrell et al 1999). Investigations of the I\D polymorphism in relation to physical performance in mountaineers and athletes (Montgomery et al 1998 ;Gayagay et al 1998) have given further impetus to similar studies on HA residents.…”

Section: mentioning

confidence: 99%

“…During the last few decades, a significant amount of work has been done to understand the human biology of HA adaptation and disorders (Mirrakhimov & Winslow, 1996 ;Semenza, 1999 ;Lahiri, 2000). Because of their intimate involvement, two main physiological systems have been targeted ; namely, the sympathetic-adrenalmedullary system (Mazzeo et al 1994 ;Lahiri, 2000 ;Prabhakar, 2000) and the reninangiotensin-aldosterone system (Milledge & Catley, 1987 ;Morrell et al 1999). In recent years, attention has shifted towards candidate genes, notable among them being the ACE gene (Rupert et al 1999 ;Morell et al 1999) and its insertion\ deletion (I\D) polymorphism in particular.…”

Section: mentioning

confidence: 99%

Angiotensin converting enzyme insertion allele in relation to high altitude adaptation

Pasha

Khan

Kumar

et al. 2001

Annals of Human Genetics

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Angiotensin converting enzyme (ACE) gene I\D polymorphism has been associated with high altitude (HA) disorders as well as physical performance. We, however, envisage that the polymorphism may be associated with adaptation to the hypobaric hypoxia of altitude, thus facilitating physical performance. For this purpose, three unrelated adult male groups, namely (1) the Ladakhis (HLs), who reside at and above a height of 3600 m, (2) lowlanders, who migrated to Ladakh (MLLs), and (3) resident lowlanders (LLs), have been investigated. The HLs had significantly ( p 0n001) greater numbers of the II homozygotes and the ID heterozygotes than the DD homozygotes, the genotype distribution being 0n46, 0n43 and 0n11 for II, ID and DD genotypes respectively. The MLLs comprised 60 % II homozygotes, which was higher ( p 0n001) than the HLs (46 %). In the LLs, the heterozygotes were greater ( p 0n001) in number than the II and DD homozygotes. The I allele frequency was 0n72 in the MLLs, 0n67 in the HLs and 0n55 in the LLs. Polymorphism study suggested that the II genotype could be associated with altitude adaptation, which might influence physical efficiency. People living at sea level experience various levels of physical discomfort at high altitude (HA) due to hypobaric hypoxia and cold. The effects of hypoxia on cardio-pulmonary function (Sutton et al. 1988 ; Mirrakhimov & Winslow, 1996) are most evident during hard physical work when the already taxed oxygen transport system needs to meet increased metabolic demands. This results in somewhat reduced levels of performance of individuals when faced with tasks demanding high levels of physical and mental performance. However, long-term in-

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“…In fact, by blocking its for mation still through the action of a con verting enzyme inhibitor, not only the establishment of pulmonary hypertension and the formation of right ventricular hy pertrophy are prevented, but a lowering of pulmonary arterial pressure itself occurs, too [12,15], It has been demonstrated that chronic alveolar hypoxia in rats increases the de gree of ACE activity both in the serum and on the level of the pulmonary tissue [8]. In man, too, chronic hypoxia due to pro longed altitude exposure led serum ACE activity to be elevated [6], This may lead to presume that the chronic respiratory failure of COLD pa tients may stimulate a greater ACE activ ity. Such a supposition may explain the interesting correlation (fig-2) seen in the percentage of BAP reduction in relation to the degree of hypoxemia in our patients and, therefore, in relation to the greater activity of Captopril.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, it might be expected that diffuse lung disease and pulmonary hypertension are asso ciated with alterations of ACE activity. In deed, hypoxia remarkably influences ACE activity: while acute hypoxia reduces this enzymatic action, thus preventing the formation of high levels of All and aldo sterone [6], chronic hypoxia has shown to be able to increase it [7,8].…”

Section: Introductionmentioning

confidence: 99%

Effects of Captopril on Hemodynamics and Blood Gases in Chronic Obstructive Lung Disease with Pulmonary Hypertension

Cicero

Busnardo

et al. 1986

Respiration

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The effects of Captopril, an angiotensin-converting enzyme inhibitor, on pulmonary hemodynamics and blood gases were studied in 9 patients with chronic obstructive lung disease (COLD) and pulmonary hypertension (PAP > 20 mm Hg). Hemodynamic data were recorded prior to Captopril administration (50 mg per os) and for the next 60min. Following Captopril administration, significant reductions in mean pulmonary artery pressure (PAP) (p < 0.05), in mean pulmonary wedge pressure (PWP) (p < 0.05), and in total pulmonary resistance (TPR) were noted; significant reductions in mean brachial artery pressure (BAP) and systemic vascular resistance (SVR) were also recorded, while cardiac output, heart rate and blood gas tensions showed no significant changes. Furthermore, the higher the hypoxemia, the greater was the reduction in BAP (p < 0.05). We therefore feel that Captopril, when administered to COLD patients with pulmonary hypertension, may protect the pulmonary circulation from hypoxic pulmonary vasoconstriction.

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Angiotensin converting enzyme activity and hypoxia

Cited by 25 publications

References 0 publications

The role of the renin‐angiotensin system in the renal response to moderate hypoxia in the rat.

The role of the renin‐angiotensin system in the renal response to moderate hypoxia in the rat.

Angiotensin converting enzyme insertion allele in relation to high altitude adaptation

Effects of Captopril on Hemodynamics and Blood Gases in Chronic Obstructive Lung Disease with Pulmonary Hypertension

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