The Mechanism of the Antihypertensive Action of Progesterone: Hemodynamic Studies in Rats with Partial Nephrectomy Salt Hypertension

Sušić, Dinko; Radujković, Gordana Bukara; Kentera, D.

doi:10.3109/10641968309069494

Cited by 5 publications

(1 citation statement)

References 12 publications

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“…Progesterone has been shown to decrease blood pressure in some hypertensive patients and animals, 27 n and it has been suggested that its blood pressure lowering effect may not depend on its antimineralocorticoid properties. 28 Arterial hypertension induced by the glucocorticoid RU 26988 was accompanied by an increase in total "Na efflux from vascular smooth muscle that appears to be caused exclusively by a stimulation of the sodium pump. Simultaneously, RU 26988-induced hypertension was characterized by an increase in ^Rb efflux.…”

Section: Discussionmentioning

confidence: 99%

Effects of antiglucocorticoids on glucocorticoid hypertension in the rat.

Grünfeld¹,

Eloy²,

Moura³

et al. 1985

Hypertension

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SUMMARY The early phase of hypertension induced in rats by a glucocorticoid agonist RU 26988 was studied. Systolic blood pressure increased by 35 mm Hg. Water and sodium urinary excretion increased transiently, and plasma volume decreased. Total and ouabain-sensitive sodium efflux, as well as rubidium efflux, were enhanced by glucocorticoid administration. Low salt intake did not prevent hypertension. Pretreatment with RU 38486, a steroid with antiglucocorticoid properties, largely prevented the rise in blood pressure ( + 10 mm Hg) and suppressed transient natriuresis and the decrease in plasma volume. Changes in total and ouabain-sensitive sodium efflux were completely prevented, whereas changes in rubidium efflux were only partly reversed. Similarly, administration of progesterone, a steroid with antiglucocorticoid effects, prevented glucocorticoid hypertension (+11 mm Hg) and vascular ionic changes. In contrast administration of RU 28318, an antimineralocorticoid agent, was without effect on glucocorticoid hypertension (+ 38 mm Hg). Progesterone or RU 38486 administered after glucocorticoid also decreased blood pressure. Present data indicate that glucocorticoid hypertension may be prevented or reversed in its early phase by steroid drugs with antiglucocorticoid properties. These drugs also appeared to prevent the sodium and rubidium flux abnormalities induced by glucocorticoid. We suggest that activation of the vascular glucocorticoid receptors may be involved in the pathophysiology of glucocorticoid hypertension. (Hypertension 7: 292-299, 1985 We therefore initiated a study of the in vivo effects of RU 26988 in the rat. RU 26988 is a specific glucocorticoid receptor agonist that exhibits high affinity for glucocorticoid receptor sites and does not compete with aldosterone for the mineralocorticoid receptor."12 We attempted to antagonize glucocorticoidinduced hypertension by administration of an antimineralocorticoid (RU 28318) and steroid derivatives known to bind competitively at the glucocorticoid receptor-progesterone and RU 38486. The latter steroid has mainly antiprogesterone properties; in vitro studies have also shown antiglucocorticoid activity. 13-I4 Lastly, we investigated the ionic changes induced by glucocorticoid and antiglucocorticoids on the rat tail artery after in vivo administration of the steroid drugs.

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Section: Discussionmentioning

confidence: 99%

Effects of antiglucocorticoids on glucocorticoid hypertension in the rat.

Grünfeld¹,

Eloy²,

Moura³

et al. 1985

Hypertension

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Gender-specific protection from microvessel rarefaction in female hypertensive rats

Papanek

Rieder

Lombard

et al. 1998

American Journal of Hypertension

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Epidemiologic studies reveal that women have a significantly lower age-adjusted morbidity and mortality from cardiovascular disease than men, suggesting that gender is a cardiovascular disease risk factor. The mechanism of the "gender protection" is unknown. In this study, we investigated the microvascular remodeling in reduced renal mass plus a high salt (4.0% NaCl) diet model of hypertension (RRM + HS). We hypothesized that women would be protected from the increase in blood pressure and from the microvascular rarefaction associated with RRM + HS hypertension. Studies were designed to determine whether female rats were less susceptible to changes in microvessel density during RRM + HS. Microvessel density was measured in male and female low salt (0.4% LS) sham-operated controls (Sham + LS) and after 3 days or 4 weeks of RRM + HS hypertension. The microcirculation of hind limb (medial and lateral gastrocnemius, plantaris, soleus) muscles was visualized using rhodamine-labeled Griffonia simplicifolia I lectin. Tissue sections were examined by videomicroscopy and microvessel density was determined by quantitative stereology. As shown previously, mean arterial pressure increased to 160 +/- 8 mm Hg and microvessel density decreased (>30% decrease in all beds) in male RRM + HS. In contrast, mean arterial pressure of female RRM + HS rats was modestly increased from 101 +/- 2 to 118 +/- 4 mm Hg. Despite previous results showing a reduction in microvessel density of both normotensive and hypertensive male rats on a high salt diet, microvessel density of female RRM + HS rats was not reduced at either time. These results suggest that gender protection in the RRM rat extends beyond an attenuation of the increase in pressure to an immunity from microvascular rarefaction.

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Progesterone Antagonizes Development but Not Maintenance of Acth‐induced Hypertension in Sheep

Spence

Reid

Coghlan

et al. 1989

Clin Exp Pharma Physio

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1. This study investigated the effect of progesterone, which, under certain circumstances, can antagonize both the mineralocorticoid and glucocorticoid activities of steroid hormones, on the development and maintenance of adrenocorticotrophic hormone (ACTH)-induced hypertension in conscious sheep. 2. Progesterone (500 mg/day) alone, for 5 days, had no effect on blood pressure, but increased urinary Na excretion by 38 +/- 10 mmol/day (P less than 0.05) during the first 24 h. 3. Infusion of ACTH (5 micrograms/kg per day), alone, for 3 days, increased arterial pressure by 21 +/- 2 mmHg (P less than 0.001) associated with hypernatraemia, hypokalaemia, urinary Na retention, and increased fasting plasma glucose concentration. 4. Progesterone (500 mg/day) concurrently with ACTH blocked the rise in mean arterial pressure and the mineralocorticoid (urinary Na retention) but not the glucocorticoid (increase in plasma glucose concentration) effects associated with ACTH administration. 5. Progesterone (500 and 1000 mg/day) failed to reverse the hypertension and hypokalaemia in sheep pretreated for 3 days with ACTH. 6. Thus, progesterone blocked the onset but did not affect established ACTH hypertension. The mechanism by which progesterone blocked the development of ACTH hypertension appears to be related to the ability of progesterone to block the essential mineralocorticoid component of the adrenocortical steroids involved in the development of ACTH hypertension.

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The Mechanism of the Antihypertensive Action of Progesterone: Hemodynamic Studies in Rats with Partial Nephrectomy Salt Hypertension

Cited by 5 publications

References 12 publications

Effects of antiglucocorticoids on glucocorticoid hypertension in the rat.

Effects of antiglucocorticoids on glucocorticoid hypertension in the rat.

Gender-specific protection from microvessel rarefaction in female hypertensive rats

Progesterone Antagonizes Development but Not Maintenance of Acth‐induced Hypertension in Sheep

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