The neural and hormonal control of splanchnic blood flow in normal and abnormal man.

Abstract

In this thesis the merit off a non-invasive Doppler ultrasound method of measuring superior mesenteric artery (a major constituent of the splanchnic vascular bed) blood flow in man is evaluated. The reproducibility off this method is assessed and then applied to determine the neural and humoral control off the splanchnic vascular bed in normal subjects, patients with sympathetic denervation (primary autonomic failure) and essential hypertension. Sympatho-neural activation by pressor tests and head-up tilt caused marked splanchnic vasoconstriction associated with a rise (pressor tests) or maintenance (tilt) of blood pressure in normal subjects but not in patients with sympathetic denervation in whom severe postural hypotension occurred. Sympatho-inhibition by clonidine, a centrally acting ?2 adrenoreceptor agonist lowered blood pressure, caused a fall in cardiac ouput and actively dilated the mesenteric artery in normal subjects and in patients with central sympathetic denervation. In patients with peripheral sympathetic failure clonidine did not lower blood pressure or dilate the superior mesenteric artery. Alcohol ingestion lowered supine blood pressure and dilated mesenteric vessels in sympathetic denervation but not in normals. These responses could be prevented by Octreotide, a somatostatin analogue which inhibits release of gut peptides. In hypertensives the resting mesenteric vascular resistance was higher than in controls and sympatho-inhibition by clonidine reversed these changes and lowered blood pressure. In normal subjects, angiotensin converting enzyme inhibition by captopril caused active mesenteric vasodilatation but failed to lower blood pressure. Mesenteric vasoconstriction occurred during tilt indicating that captopril induced mesenteric vasodilatation was independent of sympathetic activity. These results suggest that the sympatho-neural and hormonal (renin-angiotensin and gut peptides) control of the mesenteric vascular bed is important for maintenance of blood pressure. Thus abnormal splanchnic vascular responses contributes to severe postural and post-alcohol hypotension in sympathetic denervation. Similarly a higher sympathetic activity and splanchnic vascular resistance may play a part in the pathogenesis of essential hypertension