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Ashley S Izzard

Publications and source records attributed to Ashley S Izzard.

6 recordsLinked to original sources
PubMed2006

Adenosine- and hypoxia-induced dilation of human coronary resistance arteries: evidence against the involvement of K(ATP) channels.

1. The ATP-sensitive potassium (K(ATP)) channel may be an important mediator of metabolic dilation in the human coronary circulation. As adenosine and hypoxia are considered to be major mediators of metabolic dilation in the coronary circulation, we investigated the effect of glibenclamide (a K(ATP) channel blocker) on adenosine and hypoxic dilation of human coronary resistance arteries, with myogenic tone, in vitro. 2. Vessels were dissected from the atrial appendage from consenting patients and studied in vitro using a pressure arteriograph system. Segments of coronary resistance artery were pressurized to 60 mmHg and the vessels studied developed spontaneous myogenic tone. 3. The K(ATP) opener pinacidil (final conc. 5 x 10(-6) M) resulted in dilation, which was completely reversed by 5 x 10(-6) glibenclamide (84+/-14 vs -10+/-9%, pinacidil and pinacidil plus glibenclamide, respectively, P=0.009, n=5). 4. Adenosine (final conc. 10(-5) M) resulted in dilation, glibenclamide (5 x 10(-6) and 10(-5) M) was without effect (118+/-12 vs 104+/-16% adenosine and adenosine plus 10(-5) glibenclamide, respectively, n.s., n=4). 5. Hypoxia (8+/-3 mmHg O2) resulted in a dilation that reversed when normoxic conditions were restored (60+/-9 vs 3+/-11% hypoxia and post-hypoxia, respectively, P=0.014, n=3). The hypoxic dilation was not affected by glibenclamide (63+/-14 vs 55+/-6% hypoxia and hypoxia plus glibenclamide, respectively, n.s., n=4). In a further series of experiments, vessels were incubated with glibenclamide (5 x 10(-6)) prior to a hypoxic challenge; again, glibenclamide was without effect on the hypoxic dilation (-0.008+/-2 vs 95+/-3% glibenclamide and glibenclamide plus hypoxia, respectively, P=0.0005, n=3). 6. These data demonstrate that glibenclamide is without effect on both adenosine and hypoxic dilation of human coronary resistance arteries with myogenic tone, from the right atrial appendage in vitro. Our findings suggest that the K(ATP) channel is unlikely to be a major mediator of metabolic dilation in these arteries.

Adenosine↗
PubMed2006

Middle cerebral artery structure and distensibility during developing and established phases of hypertension in the spontaneously hypertensive rat.

OBJECTIVE: The aims of the current study were to examine the structural properties of middle cerebral arteries (MCA) from young (5-7 weeks) and adult (20-24 weeks) spontaneously hypertensive rats (SHR), compared with age-matched Wistar-Kyoto (WKY) control rats. DESIGN: MCA segments (8-10 per group) were secured onto glass pipettes in a small vessel chamber and studied using a pressure arteriograph system. Vessels were perfused in Ca2+-free physiological salt solution to ensure the absence of tone. The wall thickness and lumen diameter were recorded at intraluminal pressures ranging from 3 to 180 mmHg using a video dimension analyser. RESULTS: There was a borderline increase in systolic pressure of the young SHR, compared with WKY controls, but the systolic pressure of the older SHR was significantly raised. The MCA lumen diameter from young SHR was reduced across the entire pressure range and arterial distensibility was not reduced, compared with WKY vessels. The MCA lumen diameter from adult SHR was reduced at high pressure, but converged with the lumen diameter of the WKY vessels at 3 mmHg, and the stress-strain relation was shifted to the left, compared with the WKY vessels; nevertheless, the slope of the tangential elastic modulus-stress relation was not significantly increased. The pressure-wall cross-sectional area relationship did not differ between strains at either time point. CONCLUSIONS: These data demonstrate eutrophic inward remodelling of the MCA from young SHR, compared with WKY controls. In the adult SHR the structural changes are probably a consequence of a reduced arterial distensibility.

Aging↗
PubMed2005

Small artery structure and hypertension: adaptive changes and target organ damage.

Hypertension is known to be associated with an increase in the wall/lumen ratio (W/L) of the resistance arteries. Growth, eutrophic remodelling and changes in arterial distensibility can all contribute to an increase W/L. Wall stress may stimulate growth, whereas remodelling and/or reduced distensibility may be the result of prolonged contraction. Impaired or overwhelmed pressure-induced myogenic constriction, causing increased wall stress, may explain the small artery growth seen in diabetes and secondary hypertension, respectively. We find that small artery growth is a greater predictor of cardiovascular events than an increased W/L.

Adaptation, Physiological↗
PubMed2003

Myogenic and structural properties of cerebral arteries from the stroke-prone spontaneously hypertensive rat.

The aims of the study were to compare the myogenic and structural properties of middle cerebral arteries (MCAs) from the stroke-prone spontaneously hypertensive rat (SHRSP) with MCAs from the spontaneously hypertensive rat (SHR) before stroke development in SHRSP. Rats were fed a "Japanese" diet (low-protein rat chow and 1% NaCl in drinking water) for 8 wk, and cerebral arteries were studied in vitro at 12 wk using a pressure arteriograph. Systolic pressure was significantly increased in SHRSP compared with SHR at 12 wk. Between 60 and 180 mmHg, MCAs from SHR maintained an essentially constant diameter, i.e., displayed a "myogenic range," whereas the diameter of MCAs from SHRSP progressively increased as a function of pressure. Passive lumen diameter of MCAs from SHRSP was reduced at high pressure, and wall thickness and wall/lumen were increased, compared with SHR. Wall cross-sectional area was also increased in MCAs from SHRSP compared with the SHR, indicating growth. The stress-strain relationship was shifted to the left in MCAs from SHRSP, indicating decreased MCA distensibility compared with SHR. However, collagen staining with picrosirius red revealed a redistribution of collagen to the outer half of the MCA wall in SHRSP compared with SHR. These data demonstrate impaired myogenic properties in prestroke SHRSP compared with SHR, which may explain stroke development. The structural differences in MCAs from SHRSP compared with SHR were a consequence of both growth and a reduced distensibility.

Animals↗