Endothelin Antagonism in ANCA Vasculitis

Vasculitis patients and healthy controls matched for age, sex will be enrolled into the study. Patients will attend for 4 study days >1 week apart, whereas controls will attend for single day. Circulating Mφ and other immune cells will be confirmed using FACS prior each study.

Study 1 Both patients and control will attend for visit 1: assessment of vascular function using forearm plethysmography as part of case control study.

Vasculitis patients will then attend for visits 2, 3 & 4 as part of randomised three way crossover study (randomised & infusions given in a double-blind method): comparison of the effects of selective ETA receptor antagonism (BQ123; 1000nmol/min for 15min iv), mixed ETA/B antagonism (BQ123/788; 1000 nmol/min & 300 nmol/min for 15 min), and placebo on systemic haemodynamics.

Inclusion criteria

• Male or female
• Age 18 years and over
• Body mass index ≤35
• Normal serum albumin

Exclusion criteria

• Subject with diabetes or current smoking or chronic kidney disease (eGFR <60ml/min)
• Subject with pre-existing cardiovascular disease
• Subject is below the age of legal consent, or is mentally or legally incapacitated
• History of multiple and/or severe allergic reactions to drugs (including study drugs)
• The subject has donated blood (450 ml) within the last 4 weeks
• Past or present drug or alcohol abuse including intravenous drug abuse at any time
• Participation in another clinical trial within 1 month
• Considered to be at high risk of HIV or hepatitis B
• Women of child-bearing potential (only women who are post-menopausal or surgically-sterilised will be included in the study)