Failure of chronic aldosterone infusion to increase arterial pressure in dogs with angiotensin-induced hypertension.

Lohmeier, Thomas E.; Cowley, Allen W.; DeClue, J W; Guyton, Arthur C.

doi:10.1161/01.res.43.3.381

Cited by 23 publications

(25 citation statements)

References 28 publications

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“…The aldosterone levels in the 2 groups were similar, yet the blood pressures remained lower in the D + R -group lacking extrarenal AT 1A receptors, compared with those in D + R + controls ( Figure 6B). These findings corroborate other studies in which infusion of aldosterone alone failed to raise blood pressure (35) and suggest that the adrenal gland is not a critical site for blood pressure control by extrarenal AT 1A receptors. We speculate instead that AT 1A receptors in the CNS and/or in the vasculature are more likely to mediate the component of blood pressure regulation that is independent of the kidney.…”

Section: Figuresupporting

confidence: 90%

Distinct roles for the kidney and systemic tissues in blood pressure regulation by the renin-angiotensin system

Crowley¹,

Gurley²,

Oliverio³

et al. 2005

J. Clin. Invest.

275

115

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Angiotensin II, acting through type 1 angiotensin (AT 1 ) receptors, has potent effects that alter renal excretory mechanisms. Control of sodium excretion by the kidney has been suggested to be the critical mechanism for blood pressure regulation by the renin-angiotensin system (RAS). However, since AT 1 receptors are ubiquitously expressed, precisely dissecting their physiological actions in individual tissue compartments including the kidney with conventional pharmacological or gene targeting experiments has been difficult. Here, we used a cross-transplantation strategy and AT 1A receptor-deficient mice to demonstrate distinct and virtually equivalent contributions of AT 1 receptor actions in the kidney and in extrarenal tissues to determining the level of blood pressure. We demonstrate that regulation of blood pressure by extrarenal AT 1A receptors cannot be explained by altered aldosterone generation, which suggests that AT 1 receptor actions in systemic tissues such as the vascular and/or the central nervous systems make nonredundant contributions to blood pressure regulation. We also show that interruption of the AT 1 receptor-mediated short-loop feedback in the kidney is not sufficient to explain the marked stimulation of renin production induced by global AT 1 receptor deficiency or by receptor blockade. Instead, the renin response seems to be primarily determined by renal baroreceptor mechanisms triggered by reduced blood pressure. Thus, the regulation of blood pressure by the RAS is mediated by AT 1 receptors both within and outside the kidney.

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Section: Figuresupporting

confidence: 90%

Distinct roles for the kidney and systemic tissues in blood pressure regulation by the renin-angiotensin system

Crowley¹,

Gurley²,

Oliverio³

et al. 2005

J. Clin. Invest.

275

115

View full text Add to dashboard Cite

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“…Similarly, infusion of aldosterone at this same elevated rate in dogs with All hypertension produced marked mineralocorticoid effects but no further increase in MAP. 11 In contrast, when ACTH was infused in dogs with All hypertension, MAP increased an additional 16 mm Hg (manuscript submitted for publication). Additionally, in the present study, dogs with NE hypertension were infused with very high rates of aldosterone simul-taneously with enough cortisol to increase plasma cortisol concentration to levels comparable to those achieved with ACTH.…”

Section: Discussionmentioning

confidence: 99%

“…11 The effects of aldosterone infusion on MAP, urinary sodium excretion, urinary potassium excretion, urine excretion, and water consumption are shown in figure 5. During the initial 10 days of aldosterone infusion, MAP increased progressively to 14 ± 3 mm Hg above control on Day 10.…”

Section: Effects Of Aldosterone Infusion In Normotensive Dogsmentioning

confidence: 99%

“…Further, this chronic potentiation of All hypertension by ACTH could not be reproduced by longterm infusion of high doses of either cortisol or aldosterone. 11 This suggests a hypertensinogenic effect of ACTH other than that mediated via enhanced mineralocorticoid or enhanced glucocorticoid activity. However, the arterial pressure effects of simultaneous infusion of cortisol plus aldosterone were not determined.…”

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confidence: 99%

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Chronic potentiation of vasoconstrictor hypertension by adrenocorticotropic hormone.

Lohmeier¹,

Carroll²

1982

Hypertension

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SUMMARY The chronic effects of ACTH on mean arterial pressure (MAP) and related variables were studied in dogs with both chronic norepinephrine (NE)-and chronic aldosterone-lnduced hypertension. MAP was recorded continuously for 24 hours/day, and sodium intake was 71 mEq/day. ACTH was infused for 8 days at a rate that does not increase MAP in normotensive dogs and yet a rate that produces pronounced mineralocorticoid and glucocorticoid effects. Chronic ACTH infusion in dogs with NE hypertension caused natriuresis, kaliuresis, diuresis, hypernatremia, hypokalemia, and suppression of PRA; additionally, there was either no net change in water balance or net water balance was positive. However, in marked contrast to dogs without pre-existing hypertension, in dogs with NE hypertension ACTH produced a pronounced additional increase in MAP of 39 to 63 mm Hg. Although ACTH markedly potentiated NE hypertension, high infusion rates of aldosterone (+6 mm Hg) and cortisol (-7 mm Hg) had relatively weak effects on MAP; further, in dogs with NE hypertension, the increase in MAP associated with simultaneous infusion of high rates of cortisol and aldosterone was equal to only approximately half of that produced by ACTH. In dogs with aldosterone hypertension, the changes in salt and water balance produced by ACTH were comparable to those that occurred when ACTH was administered to dogs with NE hypertension. In dogs with aldosterone hypertension, however, ACTH did not produce kaliuresis, hypernatremia, or hypokalemia; moreover, ACTH did not exacerbate aldosterone hypertension. Thus, the data indicate that the hypertensive effects of ACTH are manifested in conditions of reduced renal excretory capacity such as exist when plasma levels of the potent sodium-retaining hormone NE are inappropriately elevated. Finally, the hypertensive effects of ACTH cannot be accounted for simply on the basis of enhanced mineralocorticoid and glucocorticoid activity. hypertension produced by ACTH and adrenocortical hormones are not completely understood. The unresolved nature of ACTH-and adrenocortical-hormone hypertension is perhaps best typified by patients with Cushing's syndrome. In these patients, hypertension is a common finding, but the cause of the hypertension has been mainly conjectural.1 One hypothesis proposed to account for the hypertension of Cushing's syndrome and one that needs to be evaluated critically is that ACTH and/or adrenocortical hormones enhance the vasoconstrictor response to pressor agents like angiotensin II (All) and norepinephrine (NE).

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“…7,19,22 These studies indicated that no further changes in MAP, heart rate, urinary electrolyte excretion, and the plasma concentrations of aldosterone, sodium, and potassium after Ϸ5 days of Ang II infusion. That is, the 5-day values for these persisted for not less than 10 to 21 days of Ang II infusion.…”

Section: Experimental Protocolmentioning

confidence: 92%

Influence of Prolonged Baroreflex Activation on Arterial Pressure in Angiotensin Hypertension

et al. 2005

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Abstract-Despite recent evidence indicating sustained activation of the baroreflex during chronic infusion of angiotensin II (Ang II), sinoaortic denervation does not exacerbate the severity of the hypertension. Therefore, to determine whether Ang II hypertension is relatively resistant to the blood pressure-lowering effects of the baroreflex, the carotid baroreflex was electrically activated bilaterally for 7 days in 5 dogs both in the presence and absence of a continuous infusion of Ang II (5 ng/kg per minute) producing high physiological plasma levels of the peptide. Under control conditions, basal values for mean arterial pressure (MAP) and plasma norepinephrine concentration (NE) were 93Ϯ1 mm Hg and 99Ϯ25 pg/mL, respectively. By day 7 of baroreflex activation, MAP and NE were reduced to 72Ϯ4 mm Hg (Ϫ21Ϯ3 mm Hg) and 56Ϯ15 pg/mL, respectively, but PRA was unchanged (controlϭ0.41Ϯ0.06 ng ANG I/mL per hour). All values returned to basal levels by the end of a 7-day recovery period. After 7 days of Ang II infusion, MAP increased from 93Ϯ3 to 129Ϯ3 mm Hg, whereas NE fell from 117Ϯ15 to 86Ϯ23 pg/mL. During the next 7 days of baroreflex activation/Ang II infusion, further reductions in NE were not statistically significant, and on the final day of baroreflex activation, the reduction in MAP was only 5Ϯ1 mm Hg, compared with 21Ϯ3 mm Hg in the control normotensive state.

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Failure of chronic aldosterone infusion to increase arterial pressure in dogs with angiotensin-induced hypertension.

Cited by 23 publications

References 28 publications

Distinct roles for the kidney and systemic tissues in blood pressure regulation by the renin-angiotensin system

Distinct roles for the kidney and systemic tissues in blood pressure regulation by the renin-angiotensin system

Chronic potentiation of vasoconstrictor hypertension by adrenocorticotropic hormone.

Influence of Prolonged Baroreflex Activation on Arterial Pressure in Angiotensin Hypertension

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