How do antihypertensive drugs work? Insights from studies of the renal regulation of arterial blood pressure

Though antihypertensive drugs have been in use for many decades, the mechanisms by which they act chronically to reduce blood pressure remain unclear. Over long periods, mean arterial blood pressure must match the perfusion pressure necessary for the kidney to achieve its role in eliminating the daily intake of salt and water. It follows that the kidney is the most likely target for the action of most effective antihypertensive agents used chronically in clinical practice today. Here we review the long-term renal actions of antihypertensive agents in human studies and find three different mechanisms of action for the drugs investigated. (i) Selective vasodilatation of the renal afferent arteriole (prazosin, indoramin, clonidine, moxonidine, α-methyldopa, some Ca++-channel blockers, angiotensin-receptor blockers, atenolol, metoprolol, bisoprolol, labetolol, hydrochlorothiazide, and furosemide). (ii) Inhibition of tubular solute reabsorption (propranolol, nadolol, oxprenolol, and indapamide). (iii) A combination of these first two mechanisms (amlodipine, nifedipine and ACE-inhibitors). These findings provide insights into the actions of antihypertensive drugs, and challenge misconceptions about the mechanisms underlying the therapeutic efficacy of many of the agents

Surgical training during the COVID-19 pandemic at a designated 'cold' site: are we meeting the challenge?

INTRODUCTION There has been a marked reduction in surgical operative training opportunities during the COVID-19 pandemic. This may be improved by the establishment of 'cold' sites for NHS elective surgery. We investigated the training opportunities at a newly designated elective surgery cold site in the West Midlands, UK. METHODS An observational retrospective study was undertaken to include all gastrointestinal and urological elective surgery at a single 'cold' site during the first peak of the COVID-19 pandemic. Patient demographics, details of surgery and data relating to surgical training such as primary surgeon and portfolio index procedure were collected. Factors affecting the likelihood of trainees being the primary surgeon were analysed using logistic regression models. RESULTS There were 880 patients, with a median (interquartile range) age of 62 (48-74). Some 658 (74.8%) procedures were defined as 'index procedures' for specialty training year 4 (ST4) level: 409/509 (80.4%) for urology, 155/235 (66%) for colorectal and 94/136 (69.1%) for upper gastrointestinal (GI). Only 253/880 (28.8%) procedures were performed by a trainee as the primary surgeon: 201/509 (39.4%) for urology, 21/235 (8.9%) for colorectal and 31/136 (22.8%) for upper GI. The likelihood of a trainee being the primary surgeon was reduced for major surgery (<0.001) and for GI surgery when compared with urology (<0.001). CONCLUSIONS Surgical training was facilitated at an elective surgery 'cold' site during the COVID-19 pandemic, but at lower levels than anticipated. Type of surgery influenced trainee participation. Surgical training should be incorporated into 'cold' site elective surgical services if trainees are to be prepared for the future