Arteriolar dilation to endothelium-derived relaxing factor (EDRF) is suppressed early in diabetes mellitus. The purpose of this study was to determine whether acute exposure to a hyperglycemic media can suppress EDRF function of normal arterioles. Dilation of intestinal arterioles to iontophoretically applied acetylcholine (ACh) and nitroprusside was measured in normoglycemic rats before and after 1 h of topical exposure to isotonic solutions containing D-glucose concentrations of 200, 300, and 500 mg/100 ml. Exposure to a D-glucose concentration of 200 mg/100 ml had no effect on vasodilation to ACh. D-Glucose concentrations of both 300 and 500 mg/100 ml caused significant suppression of the responses: for example, at the approximate 50% effective dosage (100 nA), the dilatory response was decreased by 60% at a D-glucose concentration of 300 mg/100 ml and 55% at a D-glucose concentration of 500 mg/100 ml. Responses to nitroprusside were not significantly (P < 0.05) impaired after exposure to D-glucose concentrations of 200, 300, or 500 mg/100 ml. Exposure to an isotonic L-glucose concentration of 500 mg/100 ml for 1 h had no significant (P > 0.05) effect on responses to ACh. Pretreatment with superoxide dismutase, catalase, indomethacin, or meclofenamic acid preserved EDRF-mediated vasodilation during exposure to a D-glucose concentration of 500 mg/100 ml at almost all the ACh dosages tested. These results indicate that oxygen radicals formed in part by increased eicosanoid synthesis during exposure to D-glucose hyperglycemia interfere with the EDRF mechanism before its action on the microvascular smooth muscle.

This study tested the hypothesis that both structural and functional adaptations of arterioles occur within the skeletal muscle of rats aerobically trained for 8-10 wk with treadmill exercise. The training regimen used has been shown to elicit a 37% increase in plantaris citrate synthase activity but did not result in an elevation in citrate synthase activity in the spinotrapezius or gracilis muscles of rats used in this study. In the in vivo resting spinotrapezius muscle, arteriole diameters were similar in sedentary (SED) and trained (TR) rats. However, large- (1A) and intermediate- (2A) sized arterioles dilated proportionately more in TR than in SED rats during 1- to 8-Hz muscle contractions, even though the passive mechanical properties (circumference-passive wall tension relationships) were similar between groups. Vascular casts demonstrated a trend for an increase in the number of small (3A) arterioles and an approximately 20% increase in the passive diameter of 1A and 2A arterioles in the spinotrapezius muscle of TR rats. In contrast, in the gracilis muscle, arteriole diameters and density were identical in SED and TR rats, but the capillary-to-muscle fiber ratio was approximately 15% higher in TR rats. The results suggest that aerobic exercise training can greatly increase functional vasodilation and induce a slight increase in vascular density in skeletal muscle tissues, even if the oxidative capacity of these tissues is not increased by the training regimen.

This study evaluated the possibility that during skeletal muscle contractions tissue O2 tension (Po2) around arterioles and venules decreases substantially more than in the middle of the capillary bed and thereby influences functional hyperemia. Periarteriolar [H+] and [K+] were also measured because most large arterioles are in close proximity to venules such that the biochemical status of the periarteriolar tissue could be influenced by a large decrease in O2 availability in the annulet of tissue surrounding the venules. Stimulation frequencies in the range of 2-12 Hz were used to activate the rat spinotrapezius muscle. Periarteriolar and capillary bed Po2, [H+], and [K+] changed during the first few minutes of stimulation but were restored to near resting concentrations as the functional hyperemia developed. However, perivenular Po2 decreased rapidly to approximately 50-60% of the resting gas tension as contractions began, and only minor recovery occurred. Elevation of tissue and periarteriolar Po2 with an O2-enriched superfusion solution did not prevent dilation during contractions to the same diameter as during the response at very low superfusion Po2. Therefore, the extent to which O2 influences arteriolar dilation and exercise hyperemia in the spinotrapezius muscle of the rat may depend less on periarteriolar and capillary bed Po2 than on the release of vasoactive materials from the nearby perivenular tissues as the availability of O2 decreases.

In the rat intestinal and cerebral microvasculatures, acute D-glucose hyperglycemia suppresses endothelium-dependent dilation to ACh without affecting endothelium-independent dilation to nitroprusside. This study determined whether acute hyperglycemia suppressed arteriolar wall nitric oxide concentration ([NO]) at rest or during ACh stimulation and inhibited nitroprusside-, ACh- or contraction-induced dilation of rat spinotrapezius arterioles. Vascular responses were measured before and after 1 h of topical 300 mg/100 ml D-glucose; arteriolar [NO] was measured with NO-sensitive microelectrodes. Arteriolar dilation to ACh was not significantly altered after superfusion of 300 mg/100 ml D-glucose. However, after hyperglycemia, arteriolar [NO] was not increased by ACh, compared with a 300 nM increase attained during normoglycemia. Arteriolar dilation to submaximal nitroprusside and muscle contractions was enhanced by hyperglycemia. These results indicated that in the rat spinotrapezius muscle, acute hyperglycemia suppressed arteriolar NO production while simultaneously augmenting vascular smooth muscle responsiveness to nitroprusside, presumably through cGMP-mediated mechanisms. In effect, this may have allowed ACh- and muscle contraction-induced vasodilation to be maintained during hyperglycemia despite an impaired NO system.

Arterial vessel responses to sodium nitroprusside (SNP) and acetylcholine (ACh) were measured in the spinotrapezius muscle of sedentary (Sed) and treadmill-trained (Tr) rats to determine whether these endothelium-dependent (ACh) and -independent (SNP) mechanisms contribute to the training-induced increase in functional vasodilation previously observed. Control and maximal vessel diameters were similar between Sed and Tr. After 8 wk of training, functional dilation (2-, 4-, and 8-Hz contractions) was enhanced in all orders of vessels studied [terminal feed artery (FA), largest arterioles (1A), and intermediate-sized arterioles (2A)], but responses to SNP were increased only in FA. Responses to ACh were not significantly increased in any vessel order. After 16 wk of training, functional dilation had regressed in Tr such that only the FA response to 4 Hz was significantly elevated relative to Sed. However, the FA and 1A responses to SNP were significantly greater in Tr than in Sed, as were the 1A and 2A responses to ACh. These results show a dissociation of functional dilation and SNP- or ACh-mediated responses, as well as age-dependent interactions, a time-dependent progression, and vessel order specificity in the adaptations to training.