Risk reduction by preventing stroke: need for blockade of angiotensin II and catecholamines?
Angiotensin (AT) II and noradrenaline play major roles in hypertension, stroke and coronary heart disease, which are themselves interlinked. Harmful effects of AT II are not blocked solely by angiotensin-converting enzyme inhibitors, as it is now evident that AT II is generated by other enzymes such as chymase. Angiotensin II also stimulates noradrenaline release modulated by presynaptic receptors on sympathetic nerves. Numerous studies have defined the action of the AT II type 1 receptor blocker (ARB) eprosartan as controlling noradrenergic and adrenergic effects, resulting from actions on the renin-angiotensin-aldosterone system and the sympathetic nervous system. Clinical studies have been carried out to assess the effects of ARBs on morbidity and mortality. The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial compared the effects of valsartan and the calcium channel blocker (CCB) amlodipine in over 15,000 patients at high risk of a cardiac event. Results showed that blood pressure was reduced by both treatments and cardiac mortality/morbidity was similar in both groups. By contrast, the Morbidity and mortality after Stroke, Eprosartan compared with nitrendipine for Secondary prevention (MOSES) study (n = 1405) generated results which differed from the VALUE study, in that blood pressure was reduced by both eprosartan and nitrendipine, but eprosartan reduced all cardiovascular and cerebrovascular events to a greater extent than nitrendipine. It is also possible that any delayed clinical benefit of eprosartan could be due to reverse cardiac remodelling. Eprosartan, by blocking AT II receptors, reducing noradrenaline release and blocking catecholamine actions, may, therefore, provide greater protection against vascular events than CCBs or other ARBs.
Rupp
Heinz
H
Heart Center, Department of Internal Medicine and Cardiology, Philipps University of Marburg, Germany. rupp@staff.uni-marburg.de
D000179:Acrylates / Q000494:pharmacology / Q000627:therapeutic use*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D002395:Catecholamines / Q000037:antagonists & inhibitors*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D020521:Stroke / Q000401:mortality / Q000517:prevention & control*; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
D000179:Acrylates; D047228:Angiotensin II Type 1 Receptor Blockers; D002395:Catecholamines; D007093:Imidazoles; D013777:Tetrazoles; D013876:Thiophenes; C068373:eprosartan; D000068756:Valsartan; D014633:Valine; D009638:Norepinephrine