Practical considerations of the pharmacology of angiotensin receptor blockers.

A review of the drug class of angiotensin receptor blockers (ARBs) as well as the ARBs currently available by prescription in the United States is presented. The importance of angiotensin II production by non-angiotensin-converting enzyme (non-ACE) pathways, particularly human chymase, is discussed. Emphasis is placed on the mechanism of action of ARBs and the different binding kinetics of these agents. Although all ARBs, as a group, block the AT1 receptor, they may differ in the pharmacological characteristics of their binding and be classified as either surmountable or insurmountable antagonists. Mechanisms of surmountable and insurmountable antagonism as well as possible benefits of these blocking characteristics are discussed in relation to the various ARBs. The cardiovascular effects of activation of the two main subtypes of angiotensin receptors (AT1 and AT2) are presented. In addition to their treatment of hypertension, ACE inhibitors are recognized as being effective in the management of heart failure, left ventricular hypertrophy, recurrent myocardial infarctions, and renal disease. ARBs are currently indicated only for the treatment of hypertension; however, in vitro and in vivo pharmacological studies as well as preliminary clinical data suggest that ARBs, like ACE inhibitors, may also provide effective protection against end-organ damage in these conditions.

The structure and innervation of cat knee menisci, and their relation to a "sensory hypothesis" of meniscal function.

Previous work on dog knee menisci demonstrated structural differences between the meniscal horns and the meniscal bodies (O'Connor, '76). Of particular interest was the observation that the meniscal horns possessed an abundant blood and nerve supply, while the meniscal bodies did not. The presence of nerves in the meniscal horns prompted the speculation that menisci might perform a sensory function. The present study was undertaken in order to establish whether or not similar regional differences existed in cat knee menisci, structures previously believed to lack a corpuscular mechanoreceptor system (Freeman and Wyke, '67). Differences between the meniscal horns and meniscal bodies similar to those reported in the dog were found to characterize cat knee menisci. In particular, the meniscal horns possessed a rich neurovascular supply, while the meniscal bodies did not. Most important, at least two morphologically different mechano-receptors were identified in the meniscal horns, but none were identified in the meniscal bodies.