Abnormalities of the resistance vasculature in hypertension: correction by vasodilator therapy.
The structure of the resistance vessels in patients with essential hypertension is altered, with reduction of the lumen diameter and increase in wall-to-lumen ratio without change in wall mass, known as eutrophic remodelling. The alteration appears to cause a reduction in the vascular reserve, in particular the coronary reserve (the ability to increase blood flow during hyperaemia). Successful treatment of hypertension should therefore seek not only to reduce blood pressure but also to normalize the structure of the resistance vessels. The available evidence shows that the effect of antihypertensive treatment on resistance vessel structure is variable and not related to the reduction in blood pressure. Instead it appears that the key feature allowing normalization of vascular structure is the ability of the treatment to cause a reduction in total peripheral resistance. Thus beta-blocker treatment is apparently unable to correct the abnormal vascular structure, although vasodilator treatment - for example with angiotensin coverting enzyme (ACE)-inhibitors - is able to do this. In vivo studies in rats, and in vitro organ culture experiments have suggested that the remodelling is related to the activation of the vascular smooth muscle. The process seems to be mediated at least in part by tissue transglutaminase, an enzyme which specifically controls the interaction of smooth muscle with the extracellular matrix. Taken together the data support the desirability of vasodilator therapy in the treatment of essential hypertension.
Mulvany
Michael J
MJ
Department of Pharmacology, University of Aarhus, University Park 240, 8000 Aarhus C., Denmark.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009924:Organ Culture Techniques / Q000379:methods; D051381:Rats; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D014665:Vasodilator Agents