The Pharmacology of Human Blood Vessels in vivo

Abstract

Forearm plethysmography coupled with brachial artery drug administration and the Aellig technique in hand veins coupled with local venous drug administration are both extremely powerful tools, now widely available to the clinical pharmacologist. These techniques allow precise assessment of drug effects on vascular smooth muscle in vivo, without the confounding influences of drug effects on other organs or activation of neurohumoral reflexes. These local techniques allow the direct study of human vascular physiology, pharmacology, and pathophysiology in vivo in humans. In addition, they can form an important part of the early clinical development programme for new cardiovascular drugs, including drugs affecting the renin-angiotensin system and the sympathetic nervous system, as well as the novel agents arising from research on the vascular endothelium. Given the power of these techniques, it is important to consider where studies in patient volunteers might answer particular questions better than experiments in animal models of disease.

Altered peripheral vascular responses to exogenous and endogenous endothelin-1 in patients with well-compensated cirrhosis

“…34 As yet, there are no reports of systemic studies assessing the actions of either exogenous or endogenous ET-1 in the systemic and splanchnic circulations in patients with cirrhosis, apart from a preliminary report of infusing the ET A receptor antagonist, BQ-123, in 3 patients with advanced cirrhosis and hepatorenal syndrome. Interestingly, this study showed an improvement in renal blood flow and creatinine clearance.…”

“…The combination of subsystemic and locally active intrabrachial artery infusions with bilateral FBF measurements using venous occlusion plethysmography is a powerful and reproducible method of directly assessing in vivo vascular responses to vasoactive mediators without invoking systemic effects. 33,34 All studies were performed in a quiet, temperature-controlled room maintained at 22 to 24°C. FBF was measured as previously described.…”

“…To reduce the variability of blood flow data, the ratio of flows in both arms was calculated for each time point, thereby using the noninfused arm as a contemporaneous control. 33,34 The percentage change in FBF was calculated as follows: % change in FBF ϭ 100 ϫ [(I t /NI t ) Ϫ (I b /NI b )]/(I b /NI b ); where I t and NI t are the blood flows in the infused and noninfused forearms, respectively, at a given time point (t), and I b and NI b are the blood flows in the infused and noninfused forearms, respectively, at baseline (b); time 0. FBF was expressed in mL ϫ 100 mL tissue Ϫ1 ϫ min Ϫ1 .…”

Inhibition of Neutral Endopeptidase Causes Vasoconstriction of Human Resistance Vessels In Vivo

“…Blood flow was measured in both forearms by venous occlusion plethysmography 41 by use of indium/gallium-in-Silastic gauges as previously described. 37 Recordings of forearm blood flow were made repeatedly over 3-minute periods.…”

“…To reduce the variability of blood flow data, the ratio of flows in the two arms was calculated for each time point, in effect using the noninfused arm as a contemporaneous control for the infused arm. 41 Forearm blood flow results are shown as a percentage change from basal in the ratio of blood flow between the infused and noninfused arm.…”