Effects of aging on the vasoconstrictor reactivity and potassium channel regulation of diaphragm arterioles from male and female Fischer-344 rats.

Abstract

Regional diaphragm hemodynamics are compromised with advanced age. Evidence suggests that age-related alterations in diaphragm blood flow distribution may be related to a decline in the vasoconstrictor reactivity of the diaphragm resistance vasculature. In medial costal diaphragm first order (1A) arterioles, we hypothesized that aging would be associated with blunted myogenic vasoconstriction and increased potassium (K⁺) channel modulation of myogenic tone. In young (Y) and old (O) Fischer-344 rats (n = 71), medial costal diaphragm 1A arterioles (112-220 µm) were isolated, cannulated, and pressurized via hydrostatic fluid reservoirs. Vasoconstrictor responses to increased intraluminal pressure (myogenic), potassium chloride (KCl)-induced vasoconstriction and passive pressure-diameter responses were assessed. In a separate set of arterioles, myogenic responses were evaluated in the presence and absence of the BK_Ca channel blocker iberiotoxin (IBX; 30 nM) and IBX plus the K_V channel inhibitor 4-aminopyridine (4-AP; 5 mM). Myogenic constriction was blunted (P = 0.038), and K⁺-induced constriction was decreased in medial costal 1A arterioles from O vs. Y rats (44 ± 8% vs. 58 ± 7%; P < 0.001). BK_Ca channel inhibition increased myogenic constriction to the same extent in medial costal 1A arterioles from Y and O rats whereas combined BK_Ca and K_V channel blockade abolished the age-related differences in myogenic constriction. In medial costal diaphragm arterioles, aging is associated with: 1) impaired myogenic and K⁺-induced vasoconstriction, and 2) increased K_V channel modulation of myogenic tone. These alterations in vasoconstrictor function provide novel vascular mechanisms contributing to age-related diaphragm blood flow dysregulation.NEW & NOTEWORTHY This investigation demonstrates that old age blunts both the myogenic response and potassium (K⁺)-induced vasoconstriction of diaphragm arterioles from male and female rats. The age-related decline in myogenic constriction was due, in part, to increased voltage-gated K⁺ channel (K_V) modulation of myogenic tone. These findings provide one mechanistic basis for the impaired diaphragm blood flow distribution associated with old age and, potentially, increased fatigability.