Endothelial Dysfunction in Hypertension Is Independent From the Etiology and From Vascular Structure

Abstract

Abstract-The amI of our study was to evaluate the relatlonshlps between endothehal function, small resistance artery structure, and blood pressure m patients with primary or secondary hypertension Sixty subJects were included m the study 9 patients with pheochromocytoma, 10 with primary aldosteromsm, 17 with renovascular hypertension, and 13 with essential hypertension with 11 normotenslve subjects who served as controls Chmc and 24-hour ambulatory blood pressure (ABPM) were evaluated All subjects were submitted to a biopsy of subcutaneous fat Small resistance arteries were dissected and mounted on a mlcromyograph and the media/lumen ratio was calculated A dose-response curve to acetylcholme was performed at cumulative concentrations from lo-" to 10m5 mol/L The vasodllator response to acetylcholme was slmllarly Impaired m the four groups of hypertensive patients (ANOVA P< 05 versus normotenslve controls), without any significant difference among them In subcutaneous small arteries of patients with either primary aldosteromsm or renovascular hypertension, a marked increase m media lumen ratio was observed, whrle m patients with pheochromocytoma, the extent of vascular structural alterations was similar to that observed m essential hypertension No slgmficant correlation between media-lumen ratio or chmc blood pressure and maximum acetylcholme-induced vasodllatatlon was observed On the contrary, a significant, albelt not very close, correlation between ABPM values and maximum acetylchohne-induced vasodllatatlon was observed (r=34, P< 05 with 24-hour systolic blood pressure, r=O 36, P< 05 with 24-hour dlastohc blood pressure) In conclusion, endothehal dysfunction seems to be mdependent from the degree of vascular structural alterations and from the etiology of hypertension, and it 1s probably more linked to the hemodynamlc load (Hypertension. 1998;31[part 2]:335-341.)Key Words: acetylcholme n endothelmm w EDRF n nitric oxide I vascular resistance w hypertrophy n secondary hypertension E ndothehal cells are known to have important regulatory effects on the cardiovascular system through the release of vasodllator and vasoconstnctor mediators " In small resistance arteries, endothehum seems to have a key role m the imbalance between vasoconstnctlon and vasodllatatlon ' An impairment of the endothehal function, as evaluated by the vasodllator response to acetylcholme, has been detected m human small resistance arteries both m essentla13" and m secondary hypertension ' 5Structural abnormahtles of the media of the resistance vessels are common accompamments of chronic hypertension, and they play an Important role m the mcrease of vascular reststance, and, therefore, m the maintenance of high blood pressure values " We have previously demonstrated that the extent and the charactenstlcs of structural alterations observed m subcutaneous small resistance arteries of patients with primary or secondary forms of hypertension are not umform 4 In particular, m patients with either primary aldosteromsm or renovascular hypertension,...

Role of Heme Oxygenase in Modulating Endothelial Function in Mesenteric Small Resistance Arteries of Spontaneously Hypertensive Rats

“…In small arteries (< 350 μm of lumen diameter), the endothelium exerts a key role in the imbalance between vasoconstriction and vasodilatation and may induce growth responses in the tunica media of the vessels (5,6). Consequently, endothelial dysfunction and damage may theoretically have an impact on vascular smooth muscle cell structure and function, intercellular matrix proteins, and, hence, on small artery remodelling, although this point is still controversial (7).…”

Renal Damage in Primary Aldosteronism

“…6,7 This view has, however, been challenged by recent data. 3,8 PA has in fact been associated with widespread tissue fibrosis, 9 vascular remodeling, 10 and excess prevalence of left ventricular hypertrophy and diastolic dysfunction 11 that were corrected by adrenalectomy. 12 A higher incidence of cardiovascular complications, including atrial fibrillation, has also been described.…”

Plasma membrane calcium ATPases (PMCAs) as potential targets for the treatment of essential hypertension

“…Indeed, in some studies endothelium-dependent relaxation of resistance arteries has been reported to be preserved in hypertension by an NOS-dependent mechanism (Kang et al, 2007). Other studies have shown that abnormal endothelial function in small blood vessels does not predict cardiovascular events in patients with essential hypertension (Rizzoni et al, 2006) and indeed such dysfunction appears to be independent of vascular structural changes in hypertension (Rizzoni et al, 1998). There continues to be debate as to the role of the endothelium in the development and progression of hypertension (Luscher, 1994), nevertheless, the endothelium is an important modulator of vascular contractility and BP which should not be ignored when developing new therapeutic targets for hypertension.…”