Aldosterone acts on the kidney, not the brain, to cause mineralocorticoid hypertension in sheep

León, L. A. Sosa; McAllen, Robin M.; May, Clive

doi:10.1097/00004872-200206000-00034

Cited by 9 publications

(4 citation statements)

References 14 publications

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“…These findings are consistent with previous studies in rats by Gomez-Sanchez and Gomez-Sanchez (10). In contrast, chronic intracerebroventricular infusion of aldosterone in sheep did not change BP (22). The latter studies used regular aCSF, and it is tempting to speculate that sheep also may respond to intracerebroventricular aldosterone if combined with a small increase in CSF Na ϩ .…”

Section: Discussionmentioning

confidence: 97%

Brain sodium channels and ouabainlike compounds mediate central aldosterone-induced hypertension

Wang

Huang

Leenen

2003

American Journal of Physiology-Heart and Circulatory Physiology

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Central nervous system (CNS) effects of mineralocorticoids participate in the development of salt-sensitive hypertension. In the brain, mineralocorticoids activate amiloride-sensitive sodium channels, and we hypothesized that this would lead to increased release of ouabainlike compounds (OLC) and thereby sympathetic hyperactivity and hypertension. In conscious Wistar rats, intracerebroventricular infusion of aldosterone at 300 or 900 ng/h in artificial cerebrospinal fluid (aCSF) with 0.145 M Na+ for 2 h did not change baseline mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), or heart rate (HR). Intracerebroventricular infusion of aCSF containing 0.16 M Na+ (versus 0.145 M Na+ in regular aCSF) did not change MAP or RSNA, but significant increases in MAP, RSNA, and HR were observed after intracerebroventricular infusion of aldosterone at 300 ng/h for 2 h. Intracerebroventricular infusion of aCSF containing 0.3 M Na+ increased MAP, RSNA, and HR significantly more after intracerebroventricular infusion of aldosterone versus vehicle. After intracerebroventricular infusion of aldosterone, the MAP, RSNA, and HR responses to intracerebroventricular infusion of aCSF containing 0.16 M Na+ were blocked by blockade of brain OLC with intracerebroventricular infusion of Fab fragments or of brain sodium channels with intracerebroventricular benzamil. Chronic intracerebroventricular infusion of aldosterone at 25 ng/h in aCSF with 0.15 M Na+ for 2 wk increased MAP by 15-20 mmHg and increased hypothalamic OLC by 30% and pituitary OLC by 60%. Benzamil blocked all these responses to aldosterone. These findings indicate that in the brain, mineralocorticoids activate brain sodium channels, with small increases in CSF Na+ leading to increases in brain OLC, sympathetic outflow, and blood pressure.

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Section: Discussionmentioning

confidence: 97%

Brain sodium channels and ouabainlike compounds mediate central aldosterone-induced hypertension

Wang

Huang

Leenen

2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…32 Furthermore, inhibition of sympathetic activity has also been reported following induction of mineralocorticoid hypertension in dogs, sheep, and humans. 19,33–34 Of particular relevance to primary aldosteronism, several studies 18,20,35 but not all, 22 have reported either normal or suppressed levels of sympathetic activity in this form of secondary hypertension. Also the present study does not provide statistically significant evidence to support the hypothesis of sympathetic activation in aldosterone hypertension, in fact, even showing a small statistically insignificant reduction in plasma levels of NE during aldosterone infusion.…”

Section: Discussionmentioning

confidence: 99%

Global- and Renal-Specific Sympathoinhibition in Aldosterone Hypertension

et al. 2015

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Recent technology for chronic electrical activation of the carotid baroreflex and renal nerve ablation provide global and renal-specific suppression of sympathetic activity, respectively, but the conditions for favorable antihypertensive responses in resistant hypertension are unclear. Because inappropriately high plasma levels of aldosterone are prevalent in these patients, we investigated the effects of baroreflex activation and surgical renal denervation in dogs with hypertension induced by chronic infusion of aldosterone (12µg/kg/day). Under control conditions, basal values for mean arterial pressure and plasma norepinephrine concentration were 100±3 mm Hg and 134±26 pg/mL, respectively. By day 7 of baroreflex activation, plasma norepinephrine was reduced by ~ 40% and arterial pressure by 16±2 mmHg. All values returned to control levels during the recovery period. Arterial pressure increased to 122±5 mm Hg concomitant with a rise in plasma aldosterone concentration from 4.3±0.4 to 70.0±6.4 ng/dL after 14 days of aldosterone infusion, with no significant effect on plasma norepinephrine. After 7 days of baroreflex activation at control stimulation parameters, the reduction in plasma norepinephrine was similar but the fall in arterial pressure (7±1 mmHg) was diminished (~ 55%) during aldosterone hypertension as compared to control conditions. Despite sustained suppression of sympathetic activity, baroreflex activation did not have central actions to inhibit either the stimulation of vasopressin secretion or drinking induced by increased plasma osmolality during chronic aldosterone infusion. Finally, renal denervation did not attenuate aldosterone hypertension. These findings suggest that aldosterone excess may portend diminished blood pressure lowering to global and especially renal-specific sympathoinhibition during device-based therapy.

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“…Most experimental and clinical studies indicate that mineralocorticoid-induced hypertension is not associated with increased sympathetic activity (9,46,55,57,59 Time (Days) 62 …”

Section: Additive Blood Pressure-lowering Effects Of Renal Denervatiomentioning

confidence: 99%

Renal denervation for the treatment of resistant hypertension: review and clinical perspective

Iliescu

Lohmeier

Tudorancea

et al. 2015

American Journal of Physiology-Renal Physiology

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When introduced clinically 6 years ago, renal denervation was thought to be the solution for all patients whose blood pressure could not be controlled by medication. The initial two studies, SYMPLICITY HTN-1 and HTN-2, demonstrated great magnitudes of blood pressure reduction within 6 mo of the procedure and were based on a number of assumptions that may not have been true, including strict adherence to medication and absence of white-coat hypertension. The SYM-PLICITY HTN-3 trial controlled for all possible factors believed to influence the outcome, including the addition of a sham arm, and ultimately proved the demise of the initial overly optimistic expectations. This trial yielded a much lower blood pressure reduction compared with the previous SYMPLICITY trials. Since its publication in 2014, there have been many analyses to try and understand what accounted for the differences. Of all the variables examined that could influence blood pressure outcomes, the extent of the denervation procedure was determined to be inadequate. Beyond this, the physiological mechanisms that account for the heterogeneous fall in arterial pressure following renal denervation remain unclear, and experimental studies indicate dependence on more than simply reduced renal sympathetic activity. These and other related issues are discussed in this paper. Our perspective is that renal denervation works if done properly and used in the appropriate patient population. New studies with new approaches and catheters and appropriate controls will be starting later this year to reassess the efficacy and safety of renal denervation in humans. denervation; hypertension; pathophysiology; renal nerves; resistance RESISTANT HYPERTENSION IS defined as failure to achieve a guideline-driven blood pressure of less than 140/90 mmHg in patients who are adherent to maximally tolerated doses of at least three antihypertensive drugs, including a diuretic appropriate for kidney function (13). Population-based studies published over the last decade indicate that anywhere from 3 to 12% of hypertensive patients in the United States have resistant hypertension, despite the abundance of efficacious blood pressure-lowering agents belonging to over seven drug classes (11,20,68). Moreover, in addition to the cardiovascular mortality risk directly linked to the extent of blood pressure elevation, resistant hypertensive patients frequently have additional risk factors such as obesity, diabetes, chronic kidney disease, and age over 55 and are therefore more likely to die from stroke, myocardial infarction, heart failure, and end-stage renal disease (47, 76).Since increased sympathetic activity was believed to be present in many patients with resistant hypertension, renal denervation was thought to be the solution for all patients whose blood pressure could not be controlled by medication and was introduced for clinical use 6 years ago. In the open label, uncontrolled SYMPLICITY HTN-1 and SYMPLICITY HTN-2 trials, undertaken in patients with resistant hypertension, redu...

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Aldosterone acts on the kidney, not the brain, to cause mineralocorticoid hypertension in sheep

Abstract: In conscious sheep the hypertensive response to aldosterone resulted from an action on the kidney, with no evidence for a direct action on the brain.

Cited by 9 publications

References 14 publications

Brain sodium channels and ouabainlike compounds mediate central aldosterone-induced hypertension

Brain sodium channels and ouabainlike compounds mediate central aldosterone-induced hypertension

Global- and Renal-Specific Sympathoinhibition in Aldosterone Hypertension

Renal denervation for the treatment of resistant hypertension: review and clinical perspective

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