Vasculature Endothelial Dysfunction

In a rat model of CHF, the addition of spironolactone to ACE inhibitor therapy normalized nitric oxide-mediated endothelial relaxation by beneficially modulating the balance of nitric oxide and superoxide anion formation (41). In the New Zealand rabbit, eplerenone improved endothelial function and reduced free radical stress in early atherosclerosis (42). In vitro studies suggest that aldosterone causes non-genomic vasoconstriction of rabbit pre-glomerular afferent arterioles via the protein kinase C and inositol (1,4,5)-triphosphate (IP3) pathways (9). This effect of aldosterone, which

Mineralocorticoid Receptor

Fig. 3. Aldosterone-mediated cardiac damage. (A) Myocardial necrotic lesions (arrowheads) develop in rats treated with a high-salt diet, Ang II, and the nitric oxide synthase inhibitor L-NAME. (B) Necrotic lesions are markedly reduced when these animals are adrenalectomized or are simultaneously receiving the mineralocorticoid receptor antagonist eplerenone. Panel B is also representative of histological sections from control animals fed a high-salt diet (HSE; magnification, x340). (Reproduced from ref. 33 with permission.)

Fig. 3. Aldosterone-mediated cardiac damage. (A) Myocardial necrotic lesions (arrowheads) develop in rats treated with a high-salt diet, Ang II, and the nitric oxide synthase inhibitor L-NAME. (B) Necrotic lesions are markedly reduced when these animals are adrenalectomized or are simultaneously receiving the mineralocorticoid receptor antagonist eplerenone. Panel B is also representative of histological sections from control animals fed a high-salt diet (HSE; magnification, x340). (Reproduced from ref. 33 with permission.)

Mineralocorticoid Receptor

Fig. 4. Aldosterone-mediated coronary artery injury. Coronary arteries from mice treated with Ang II and L-NAME (A,C,E) and control animals (B,D,F). The Ang II/L-NAME animals develop fibrinoid necrosis of the vessel wall with intimal thickening, a mixed inflammatory response, and PAI-1 immunostaining. (A and B) H&E; (C and D) Masson's trichrome; (E and F) PAI-1 H135 antibody staining. Magnification, x225; bars = 50 |im. (Reproduced from ref. 34 with permission.)

Fig. 4. Aldosterone-mediated coronary artery injury. Coronary arteries from mice treated with Ang II and L-NAME (A,C,E) and control animals (B,D,F). The Ang II/L-NAME animals develop fibrinoid necrosis of the vessel wall with intimal thickening, a mixed inflammatory response, and PAI-1 immunostaining. (A and B) H&E; (C and D) Masson's trichrome; (E and F) PAI-1 H135 antibody staining. Magnification, x225; bars = 50 |im. (Reproduced from ref. 34 with permission.)

Necrosis Endotelial

Fig. 5. Aldosterone-mediated renal damage. (A) Arterial myointimal proliferation and transmural fibrinoid necrosis (arrowheads) and glomerular thrombosis (arrows) with obliteration of the capillary lumen in rats treated with a high-salt diet, Ang II, and the nitric oxide synthase inhibitor, L-NAME. (B) Necrotic lesions are markedly reduced when these animals are adrenalectomized or are simultaneously receiving the mineralocorticoid receptor antagonist, eplerenone. Panel B is also representative of histological sections from control animals fed a high-salt diet (periodic acid, Schiff; magnification, x340). (Reproduced from ref. 33 with permission.)

Fig. 5. Aldosterone-mediated renal damage. (A) Arterial myointimal proliferation and transmural fibrinoid necrosis (arrowheads) and glomerular thrombosis (arrows) with obliteration of the capillary lumen in rats treated with a high-salt diet, Ang II, and the nitric oxide synthase inhibitor, L-NAME. (B) Necrotic lesions are markedly reduced when these animals are adrenalectomized or are simultaneously receiving the mineralocorticoid receptor antagonist, eplerenone. Panel B is also representative of histological sections from control animals fed a high-salt diet (periodic acid, Schiff; magnification, x340). (Reproduced from ref. 33 with permission.)

appears to be modulated by endothelium-derived nitric oxide, has been postulated to contribute to hypertension by elevating renal vascular resistance in cardiovascular diseases associated with endothelium dysfunction.

Aldosterone also causes endothelial dysfunction in humans. For example, a 4-h systemic aldosterone infusion in young healthy volunteers induces endothelial dysfunction (43). In patients with CHF, treatment with an MR antagonist for 4 wk improved endothelial function, increased nitric oxide bioactivity, and further inhibited vascular angiotensin I/Ang II conversion in the presence of chronic ACE inhibition (44).

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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