Decreased PO₂ and Rabbit Aortic Smooth Muscle Mechanics

Abstract

Rabbit thoracic aorta was used to determine the effects of decreasing PO₂ on the mechanical properties of contractions in response to norepinephrine (NE) and KC1. Aortae were aerated with 45% O₂/5% CO₂/50% N₂ and stimulated with 10 µM NE or 50 mM KCl. At 5 min of stimulation, 5% CO₂/95% N₂aeration was introduced for 15 min, defined as hypoxia. This time period was previously shown to produce similar decrease in [ATP] in either stimulation condition. Force, stiffness and isotonic shortening velocity were monitored during the initial stimulation, during hypoxia and during re-oxygenation. Hypoxia produced a substantial and rapid decrease in force and a concomitant decrease in stiffness during NE stimulation; delayed and smaller decreases in force and stiffness were observed during KC1 stimulation. The force-stiffness relationship was steeper during KC1 than NE stimulation, and hypoxia did not affect these relationships. Isotonic shortening velocity was significantly depressed by hypoxia during both stimulations although the decrease during KC1 stimulation required a longer time. These data demonstrate that relaxation of an agonist-induced contraction in response to hypoxia results from a decrease in the number of activated crossbridges and not formation of rigor bridges.

Involvement of L-Type Calcium Channels in Hypoxic Relaxation of Vascular Smooth Muscle

“…Whereas our studies suggest an effect of hypoxia on vascular smooth muscle L-type Ca 2+ channels, other investigators [10, 12, 30] have concluded that hypoxia may elicit relaxation by interfering with energy-dependent reactions in the contractile pathway, such as the production of inositol 1,4,5-trisphosphate [12] or a decrease in the formation of activated crossbridges [10]. These mechanisms are most likely to be in operation when the PO 2 is low, below the threshold for proper function of mitochondrial electron transport.…”

“…Indeed, it was under moderate hypoxia that inhibition of K ATP channels with glibenclamide had the most pronounced effect on the hypoxic relaxation response. Another possibility is that hypoxic relaxation operates through different mechanisms, depending upon the vascular bed and the nature of the stimulus used for contraction [9, 10, 32]. …”

“…In addition, hypoxia has been reported to stimulate the release of relaxing factors by the endothelium [5, 6, 7]. However, many reports indicate that vascular smooth muscle studied in isolation, in the absence of parenchymal tissues, is capable of relaxing in response to hypoxia [e.g., 8, 9, 10, 11]. Thus, it appears likely that a mechanism inherent to vascular smooth muscle is partially responsible for relaxation in response to hypoxia.…”

“…One possibility is that hypoxia interferes with a link between energy production and force development in vascular smooth muscle [10, 12, 13]. However, this requires that cellular respiration is compromised, an event which occurs only when the PO 2 is very low [14, 15, 16].…”

Moderate Hypoxia Increases Heat Shock Protein 90 Expression in Excised Rat Aorta

“…The mechanisms by which reduced oxygen tension alters vasoreactivity have been investigated extensively and found to differ depending on species, size and location of the vessel [16, 17, 18], severity of the hypoxic insult [19], and contractile stimulus [20, 21]. This study was not designed to determine the mechanism of the hypoxia-induced alteration in contractile force, but rather to evaluate the effect of a moderate hypoxic stress on HSP90 expression and to confirm that the hypoxic stress affected contractile function in excised rat aorta.…”