Angiotensinogen and angiotensin-converting enzyme gene copy number and angiotensin and bradykinin peptide levels in mice

Alexiou, Theodora; Boon, Wee Ming; Denton, Derek A.; Nicolantonio, R. Di; Walker, Lesley; Campbell, Duncan J.

doi:10.1097/01.hjh.0000166834.32817.41

Cited by 37 publications

(44 citation statements)

References 49 publications

(108 reference statements)

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“…A marked increase of baseline Fos-IR was observed in the commissural and medial parts of the NTS and also the area postrema in AgtϪ/Ϫ mice compared with WT mice. This is not surprising in view of the lower arterial blood pressure that has been reported to occur in AgtϪ/Ϫ mice (1,22,48), the importance of these two regions in cardiovascular control mechanisms (9), and previous reports of increased Fos expression in these regions caused by hypotensive stimuli (4,34).…”

Section: Discussionmentioning

confidence: 82%

“…Another possibility is that a nonangiotensin ligand that could bind to AT 1 receptors may be released upon stimulation of central osmoreceptors. Evidence of a nonangiotensin ligand partially purified from sheep hypothalamus that can bind to AT 1 and AT 2 receptors, shows the feasibility of this suggestion. It is also possible that the AT 1 receptor could be activated without a ligand, for instance by physical changes.…”

Section: Discussionmentioning

confidence: 84%

“…A possible explanation for this disparity in results is that PEG treatment caused a greater nonspecific debilitation in AgtϪ/Ϫ mice compared with WTs treated with PEG. Arterial pressure is already 20 mmHg lower in the AgtϪ/Ϫ mice than in WT mice (1,22,48) and could be expected to have fallen much further with PEG treatment in the null mice, because they lack a functioning renin-angiotensin system to support arterial pressure. Clearly there was a deleterious effect of PEG treatment in AgtϪ/Ϫ mice at some stage, because both water and NaCl intakes fell significantly below baseline in the subsequent 24 h, and three of the five AgtϪ/Ϫ mice died 24 -48 h after treatment.…”

Section: Discussionmentioning

confidence: 99%

“…If there is not, it is difficult to explain why centrally administered AT 1 antagonists inhibit drinking stimulated by intracerebroventricular injection of hypertonic saline in several species that include mice. As mentioned above, the explanation could be that either AT 1 antagonists are nonspecific, blocking another receptor, or that they block the action of a nonangiotensin molecule, which could act at the AT 1 receptor. Another possibility is that drinking stimulated by intracerebroventricular hypertonic saline is not comparable to normal osmotic thirst.…”

Section: Perspectives and Significancementioning

confidence: 99%

“…These mice exhibit lower arterial blood pressure, higher plasma renin levels, lower body weight, and an increased fluid turnover compared with wild-type (WT) mice (1,21,22,26,47,48). The lower body weight results from reduced white adipose tissue mass (26).…”

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confidence: 99%

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Osmoregulatory fluid intake but not hypovolemic thirst is intact in mice lacking angiotensin

Walker

Alexiou

Allen

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Water intakes in response to hypertonic, hypovolemic, and dehydrational stimuli were investigated in mice lacking angiotensin II as a result of deletion of the angiotensinogen gene (AgtϪ/Ϫ mice), and in C57BL6 wild-type (WT) mice. Baseline daily water intake in AgtϪ/Ϫ mice was approximately threefold that of WT mice because of a renal developmental disorder of the urinary concentrating mechanisms in AgtϪ/Ϫ mice. Intraperitoneal injection of hypertonic saline (0.4 and 0.8 mol/l NaCl) caused a similar dose-dependent increase in water intake in both AgtϪ/Ϫ and WT mice during the hour following injection. As well, AgtϪ/Ϫ mice drank appropriate volumes of water following water deprivation for 7 h. However, AgtϪ/Ϫ mice did not increase water or 0.3 mol/l NaCl intake in the 8 h following administration of a hypovolemic stimulus (30% polyethylene glycol sc), whereas WT mice increased intakes of both solutions during this time. Osmoregulatory regions of the brain [hypothalamic paraventricular and supraoptic nuclei, median preoptic nucleus, organum vasculosum of the lamina terminalis (OVLT), and subfornical organ] showed an increased number of neurons exhibiting Fos-immunoreactivity in response to intraperitoneal hypertonic NaCl in both AgtϪ/Ϫ mice and WT mice. Polyethylene glycol treatment increased Fos-immunoreactivity in the subfornical organ, OVLT, and supraoptic nuclei in WT mice but only increased Fos-immunoreactivity in the supraoptic nucleus in AgtϪ/Ϫ mice. These data show that brain angiotensin is not essential for the adequate functioning of neural pathways mediating osmoregulatory thirst. However, angiotensin II of either peripheral or central origin is probably necessary for thirst and salt appetite that results from hypovolemia.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Perspectives and Significancementioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Osmoregulatory fluid intake but not hypovolemic thirst is intact in mice lacking angiotensin

Walker

Alexiou

Allen

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Effect of the angiotensinogen genotype on experimental hypertension in mice

et al. 2007

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Polymorphisms of the angiotensinogen (Agt) gene may affect blood pressure. We used a mouse model to test for the role of the Agt genotype in low-renin or high-renin forms of hypertension. Mice bearing one, two, three, or four copies of the Agt gene underwent renal artery clipping to induce high-renin two-kidney, one-clip renovascular hypertension (2K1C), or uninephrectomy, salt loading, and application of deoxycorticosterone-acetate (DOCA) pellets to induce low-renin mineralocorticoid hypertension. Appropriate control animals were also studied. Blood pressure was measured by tail cuff as well as by direct intra-arterial recordings. There was a small effect of the Agt genotype on baseline blood pressure before induction of hypertension. The extent of 2K1C hypertension was not affected by the genotype. In contrast, there was a marked gene-dose effect on DOCA-hypertension (21.2 mmHg over all genotypes). Treatment of DOCA mice with the angiotensin II type 1 receptor antagonist abolished the genotype effect on blood pressure and left ventricular hypertrophy. There was a trend towards less suppression of endogenous aldosterone by DOCA treatment with increasing number of Agt gene copies. We conclude that the Agt genotype exerts a marked effect on blood pressure in a low-renin form of hypertension but no effect in the face of stimulated renin, at least in mice.

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Renin-Angiotensin System Phenotyping as a Guidance Toward Personalized Medicine for ACE Inhibitors: can the Response to ACE Inhibition be Predicted on the Basis of Plasma Renin or ACE?

Schilders

Boomsma

et al. 2014

Cardiovasc Drugs Ther

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Our data do not support that RAS phenotyping will help to predict the individual BP response to RAS blockade. Notably, these conclusions were reached in a carefully characterized, homogenous population, and when taking into account the known fluctuations in renin that relate to gender, age, ethnicity, salt intake and diuretic treatment, it seems unlikely that a cut-off renin level can be defined that has predictive value.

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Angiotensinogen and angiotensin-converting enzyme gene copy number and angiotensin and bradykinin peptide levels in mice

Cited by 37 publications

References 49 publications

Osmoregulatory fluid intake but not hypovolemic thirst is intact in mice lacking angiotensin

Osmoregulatory fluid intake but not hypovolemic thirst is intact in mice lacking angiotensin

Effect of the angiotensinogen genotype on experimental hypertension in mice

Renin-Angiotensin System Phenotyping as a Guidance Toward Personalized Medicine for ACE Inhibitors: can the Response to ACE Inhibition be Predicted on the Basis of Plasma Renin or ACE?

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