1 Smooth muscle membrane potential and tension measurements were made in isolated mesenteric resistance arteries from rats exposed to bacterial endotoxin (lipopolysaccharide, LPS; 10 mg kg À1 , i.p.) for 3 h to mimic septic shock syndrome. 2 Over this period, rats developed an endotoxaemic response, assessed in vivo as a 4174 mmHg drop in mean blood pressure, vascular hyporeactivity to noradrenaline (1 mg kg À1 , i.v.) and a significant increase in core body temperature. 3 In mesenteric small resistance arteries from these rats (o.d. 180 -240 mm), phenylephrine (0.01-3 mM)-evoked contraction was not altered when compared with arteries from sham-operated animals, but the concentration-relaxation curve to acetylcholine (ACh; 0.01 -3 mM) displayed a small, but significant, shift to the right. 4 The smooth muscle resting membrane potential (À70.371.6 mV) in arteries from LPS-treated rats was significantly greater than in control arteries (À55.471.2 mV), but in both cases the smooth muscle was depolarized to a similar potential by the application of N o -nitro-L-arginine methyl ester (L-NAME; 0.3 mM; À54.172.3 vs À52.472.5 mV) or glibenclamide (10 mM; À55.072.1 vs À50.472.0 mV). 5 ACh (1 mM) elicited a maximal hyperpolarization, which ranged from À14.773.2 mV (in arteries from LPS-treated rats) to -20.672.4 mV (in arteries from sham-operated rats), and was not altered by the presence of L-NAME. Levcromakalim (1 mM) increased the smooth muscle membrane potential by around À24 mV in arteries from both sets of experimental animals. 6 These results indicate that at the level of the resistance vasculature, endotoxaemia is associated with pronounced smooth muscle hyperpolarization reflecting the action of NO on K ATP channels. These changes were not associated with vascular hyporeactivity or depressed endothelial cell function in vitro, suggesting that mesenteric resistance arteries may not contribute to equivalent changes in vivo.

Q4The effects of nitroglycerin on the blood volume distribution were studied with a method of regional weighing in the anaesthetized cat. An i.v. bolus injection of nitroglycerin produced a dose-dependent decrease in arterial pressure accompanying a decrease in the thoracic blood volume. The latter change was associated with blood volume increases principally in the abdomen, and slightly in the hindquarters. Elimination of the cardiovascular reflex effects by carotid sinus denervation and cervical vagotomy significantly enhanced and prolonged the following changes: the hypotension, the decrease in thoracic blood volume and the volume pooling in the abdomen. The magnitude of increase in hindquarters blood volume was not significantly affected by the denervation procedures, but the duration was much prolonged. The results indicate that the major site of nitroglycerininduced venous pooling is in the splanchnic circulation. The peripheral venous pooling is produced at the expense of a decrease in the central or pulmonary blood volume. The secondary reflex adjustments tend to minimize the direct effects of nitroglycerin on the blood pressure and blood volume distribution.