Details

Autor(en) / Beteiligte

• Goodwill, Adam G
• Baker, Hana E
• Dick, Gregory M
• McCallinhart, Patricia E
• Bailey, Chastidy A
• Brown, Scott M
• Man, Joshua J
• Tharp, Darla L
• Clark, Hannah E
• Blaettner, Bianca S
• Jaffe, Iris Z
• Bowles, Douglas K
• Trask, Aaron J
• Tune, Johnathan D
• Bender, Shawn B

Titel

Mineralocorticoid receptor blockade normalizes coronary resistance in obese swine independent of functional alterations in K v channels

Ist Teil von

• Basic research in cardiology, 2021-12, Vol.116 (1), p.35

Ort / Verlag

Germany

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Impaired coronary microvascular function (e.g., reduced dilation and coronary flow reserve) predicts cardiac mortality in obesity, yet underlying mechanisms and potential therapeutic strategies remain poorly understood. Mineralocorticoid receptor (MR) antagonism improves coronary microvascular function in obese humans and animals. Whether MR blockade improves in vivo regulation of coronary flow, a process involving voltage-dependent K (K ) channel activation, or reduces coronary structural remodeling in obesity is unclear. Thus, the goals of this investigation were to determine the effects of obesity on coronary responsiveness to reductions in arterial PO and potential involvement of K channels and whether the benefit of MR blockade involves improved coronary K function or altered passive structural properties of the coronary microcirculation. Hypoxemia increased coronary blood flow similarly in lean and obese swine; however, baseline coronary vascular resistance was significantly higher in obese swine. Inhibition of K channels reduced coronary blood flow and augmented coronary resistance under baseline conditions in lean but not obese swine and had no impact on hypoxemic coronary vasodilation. Chronic MR inhibition in obese swine normalized baseline coronary resistance, did not influence hypoxemic coronary vasodilation, and did not restore coronary K function (assessed in vivo, ex vivo, and via patch clamping). Lastly, MR blockade prevented obesity-associated coronary arteriolar stiffening independent of cardiac capillary density and changes in cardiac function. These data indicate that chronic MR inhibition prevents increased coronary resistance in obesity independent of K channel function and is associated with mitigation of obesity-mediated coronary arteriolar stiffening.