COMBINATORIAL DRUGS

At the University of Sydney’s Westmead Applied Research Center in Australia, Professor Clara Chow's team has discovered in a long-duration study that a combination of four drugs commonly used to treat blood pressure - at only a quarter of their usual doses - is much more effective in getting blood pressure under control compared to the standard treatment with one or two drugs. The new combination could remarkably bring the blood pressure under control in 80% of the participants within 12 weeks. The four drugs were given in the form of a pill. Apart from the lower concentrations of the drugs required, ease of administering and patient compliance of the new quadruple strategy are obvious additional advantages. This discovery, published recently in Lancet, might contribute to basic changes in the management of patients having high blood pressure. Professor Chow laments that control of hypertension is not ideal anywhere, and in some regions such as Africa fewer than one in ten have it under control. The prevalence of hypertension is expected to increase to 29%(!) of the global population in four years from now

To Treat or Not to Treat (Blood Pressure)

Blood pressure is commonly elevated after a stroke. There are theoretical risks of allowing very high blood pressures, but clinical data suggest early lowering of blood pressure may worsen outcomes.

Dilating the degradome: matrix metalloproteinase 2 (MMP-2) cuts to the heart of the matter

With recent work revealing that MMPs (matrix metalloproteinases) cleave an increasingly large degradome of bioactive and signalling molecules, the dogma that MMPs are extracellular-matrix-remodelling proteases is under challenge. In this issue of the Biochemical Journal, Martínez et al. have reported that AM (adrenomedullin), a potent vasodilator predominantly expressed by blood vessel endothelial and smooth muscle cells, and microvasculature-rich tissues, is another new bioactive substrate for MMPs in vivo. Cleavage by MMP-2, but not MMP-9, generates a series of peptides; two of which retain receptor agonist and vasodilator activity, three are inactive and, excitingly, AM(11–22), a small product containing a canonical disulphide loop, is a vasoconstrictor. In view of the robust vasodilatory and other cardiac protective activities of AM in inhibiting myocardial fibrosis this represents a potent new systemic role for MMP-2 in the cardiovasculature. Hence, the paper by Martínez et al. directly implicates MMP activity in the development of hypertension and paradoxically in stimulating myocardial fibrosis, therefore pointing to exciting new possibilities for utilizing MMP-2-specific inhibitors as a new mode to treat blood pressure and heart disease.