title: Endothelial factors and microvascular hypertensive disease.
abstract: This paper discusses the role of endothelial dysfunction in human hypertension, especially in relation to small resistance artery structure, as well as the effects of anti-hypertensive drugs on endothelial function of small arteries in human and experimental hypertension. A significant impairment of endothelial function was observed in human essential hypertension as well as in secondary forms of hypertension. No correlation was observed with vascular structure. In animal models of genetic hypertension there is substantial evidence for a beneficial effect of anti-hypertensive treatment with angiotensin converting enzyme (ACE) inhibitors, calcium entry blockers and angiotensin II receptor blockers on endothelial function in small resistance arteries. A significant improvement in endothelial dysfunction may be observed in hypertensive patients after prolonged treatment with ACE inhibitors (cilazapril, lisinopril), calcium entry blockers (nifedipine), and angiotensin II receptor blockers (losartan), while atenolol and hydrochlorotiazide proved to be ineffective in this regard despite similar blood pressure reductions. We conclude that: (i) the development of hypertension is usually associated with the presence of endothelial dysfunction in small resistance arteries of essential hypertensive patients; (ii) vascular structure does not seem to be the major determinant of endothelial function, at least in subcutaneous small resistance arteries; (iii) anti-hypertensive therapy with ACE inhibitors, angiotensin II receptor blockers and calcium entry blockers may improve endothelial function; (iv) a decrease in blood pressure seems to be necessary but not sufficient to obtain a beneficial effect on the endothelium in humans.
authors.affiliation: Department of Medical and Surgical Sciences, University of Brescia, Italy. rizzoni@master.cci.unibs.it
authors.forename: D
authors.initials: D
authors.lastname: Rizzoni
authors.forename: E
authors.initials: E
authors.lastname: Agabiti-Rosei
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D017315:Cilazapril / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D017706:Lisinopril / Q000627:therapeutic use; D019808:Losartan / Q000627:therapeutic use; D009543:Nifedipine / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D017315:Cilazapril; D009569:Nitric Oxide; D017706:Lisinopril; D009543:Nifedipine; D019808:Losartan; D000109:Acetylcholine