Cheryl E. King-VanVlack

Receptor-mediated vascular and metabolic actions of endothelin-1 in canine small intestine

The effects of endothelin-1 (ET-1) infusion on blood flow (Q˙G) and O2 uptake (V˙o 2G) were examined in the small intestine of anesthetized dogs ( n = 10). Arterial and venous flows of a gut segment were isolated, and the segment was perfused at constant pressure. Arterial and gut venous blood samples were taken, gut perfusion pressure andQ˙G were measured, and O2 extraction ratio (OERG) andV˙o 2Gwere calculated. ET-1 was infused (0.118 μg ⋅ kg-1 ⋅ min-1ia) throughout the experiment. In group 1 ( n = 5), ETA receptors were blocked using BQ-123 (0.143 mg ⋅ kg-1 ⋅ min-1ia) followed by blockade of ETBreceptors with BQ-788 (0.145 mg ⋅ kg-1 ⋅ min-1ia). The order of ETA and ETB receptor blockade was reversed in group 2( n = 5). In group 1, the decrease inQ˙G observed with ET-1 infusion was partially reversed with BQ-123; no further change occurred after BQ-788 administration. In group 2, addition of BQ-788 to the infusate further decreasedQ˙G, whereas addition of BQ-123 returnedQ˙G to a value not different from that with ET-1 infusion alone. These data indicated that ET-1-induced vasoconstriction in the gut was mediated via ETA receptors and that this constriction was buffered by activation of ETB receptors.V˙o 2Gdecreased in proportion to the decrease inQ˙G with ET-1, decreased further with ET-1 plus ETB receptor blockade ( group 2), and increased in proportion to the increases in Q˙Gwith ETA receptor blockade (both groups). No changes in OERGoccurred during ETA and ETB receptor antagonism in either group. This study is the first to demonstrate that a flow-limited decrease in gutV˙o 2Goccurred with infusion of ET-1 in gut vasculature. An intriguing and novel finding was that, during O2limitation, OERG was only 50% of that normally associated with ischemia in this tissue.The effects of endothelin-1 (ET-1) infusion on blood flow (QG) and O2 uptake (VO2G) were examined in the small intestine of anesthetized dogs (n = 10). Arterial and venous flows of a gut segment were isolated, and the segment was perfused at constant pressure. Arterial and gut venous blood samples were taken, gut perfusion pressure and QG were measured, and O2 extraction ratio (OERG) and VO2G were calculated. ET-1 was infused (0.118 microgram. kg-1. min-1 ia) throughout the experiment. In group 1 (n = 5), ETA receptors were blocked using BQ-123 (0.143 mg. kg-1. min-1 ia) followed by blockade of ETB receptors with BQ-788 (0.145 mg. kg-1. min-1 ia). The order of ETA and ETB receptor blockade was reversed in group 2 (n = 5). In group 1, the decrease in QG observed with ET-1 infusion was partially reversed with BQ-123; no further change occurred after BQ-788 administration. In group 2, addition of BQ-788 to the infusate further decreased QG, whereas addition of BQ-123 returned QG to a value not different from that with ET-1 infusion alone. These data indicated that ET-1-induced vasoconstriction in the gut was mediated via ETA receptors and that this constriction was buffered by activation of ETB receptors. VO2G decreased in proportion to the decrease in QG with ET-1, decreased further with ET-1 plus ETB receptor blockade (group 2), and increased in proportion to the increases in QG with ETA receptor blockade (both groups). No changes in OERG occurred during ETA and ETB receptor antagonism in either group. This study is the first to demonstrate that a flow-limited decrease in gut VO2G occurred with infusion of ET-1 in gut vasculature. An intriguing and novel finding was that, during O2 limitation, OERG was only 50% of that normally associated with ischemia in this tissue.

ENDOTHELIAL AND SYMPATHETIC REGULATION OF VASCULAR TONE IN CANINE SKELETAL MUSCLE

In vitro studies have shown that production of the vasoconstrictor endothelin-1 (ET) is inhibited by NO in porcine aorta (Boulanger & Luscher, 1990) while in vivo studies have shown that the increase in total peripheral resistance following nitric oxide synthase (NOS) inhibition in anesthetized rats is blunted by blockade of endothelin receptors (Nafrialdi et al., 1994; Richard et al., 1995). In order to assess the role of endothelin in the regulation of resting vascular tone in skeletal muscle, it was first necessary to establish that we could effectively inhibit the vasoconstrictor actions of endothelin in our experimental preparation. Endothelin-1 binds to both ETA receptors on vascular smooth muscle producing vasoconstriction (Barnes, 1994) and to ETB receptors on endothelial cells to induce transient vasodilation through stimulation of NO production (Fujitani et al., 1993; Sakurai et al., 1992). The contribution of ETB receptors in the vasoconstrictor response to ET is minimal, but some studies have demonstrated that the ETA receptor antagonists BQ123 and FR139317 were unable to fully prevent or reverse the vasoconstrictor effect of endothelin in (Bird & Waldron, 1993; McMurdo et al., 1993). Because the dilatory action of ET is transient, we elected to focus on the vasoconstrictor action of ET.

Changes in waist circumference following haemodialysis: a brief report.

BACKGROUND Waist circumference (WC) is a known indicator of cardiovascular disease in the haemodialysis (HD) population. However it is not known if HD results in clinically significant changes in WC. OBJECTIVE The study purpose was to quantify the degree of change in WC induced by HD. METHODS This was a prospective cohort study with 27 patients on HD. Height, body weight, WC, hip circumference (HC), body mass index (BMI) and waist to hip ratio (WHR) were measured immediately prior to and following HD over three consecutive treatments. Differences between three-day average pre- and post-HD weight, BMI, WC, HC and WHR were assessed. RESULTS Post-HD WC was significantly lower than that measured pre-HD. Differences in pre-post HD body weight, BMI, HC and WHR were also observed. CONCLUSIONS All of the traditional clinical indicators of body composition (WC, HC, WHR, body weight and BMI) were lower following HD.