The vascular-disrupting agent, combretastatin-A4-phosphate, enhances neurogenic vasoconstriction in rat small arteries.

Combretastatin-A4-phosphate (CA4P/CA4), an anti-cancer drug, induces tumour hypoxia by destabilizing the cytoskeleton in tumour endothelial cells. Hypertensive side effects have been observed. We hypothesized that CA4P/CA4 lead to endothelial dysfunction followed by increased vasoconstriction.

The effect of tempol on endothelium-dependent vasodilatation and blood pressure.

High blood pressure is associated with increased oxidative stress and increased amounts of reactive oxygen species in the vascular wall which results in impairment of endothelial function and a proinflammatory state (with accelerated development of atherosclerosis). One consequence of this is a reduced nitric oxide (NO)-mediated vasodilatation which is also a prognostic marker of the severity of cardiovascular disease. Thus, improvement in endothelium-dependent vasodilatation may be an important goal in antihypertensive treatment.

Small artery remodelling in hypertension: causes, consequences and therapeutic implications.

Essential hypertension is treated primarily with a view to reducing blood pressure, and not with regard to normalizing the main pathological changes: the peripheral resistance and the cardiovascular structure. The aim of this review is to discuss whether normalization of the latter parameters, in particular resistance vessel structure, may also be a target for therapy. The review presents first the evidence for altered structure of the resistance vasculature, an increase in the media:lumen ratio of the vessels due to inward eutrophic remodelling.

Intracellular smooth muscle [Ca2+] in acetylcholine and nitric oxide-mediated relaxation of human small arteries.

In human resistance arteries the role of intracellular calcium during receptor agonist and nitric oxide (NO)-mediated vasorelaxation is almost unknown. We examined changes in smooth muscle calcium concentration ([Ca2+]i) caused by acetylcholine and the NO donor S-nitroso-N-acetylpenicillamine (SNAP) in isolated human subcutaneous small arteries. In arteries constricted with 50 mM KCl, acetylcholine and SNAP induced relaxation without any change in [Ca2+]i, whereas in noradrenaline constricted vessels, both acetylcholine and to a lesser degree also SNAP-mediated relaxation were associated with a decrease in [Ca2+]i.

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.

Pressure-induced activation of extracellular signal-regulated kinase 1/2 in small arteries.

Extracellular signal-regulated kinase 1/2 (ERK1/2) may play a central signaling role in vascular remodeling. We investigated a possible combined role for the renin-angiotensin system and platelet-derived growth factor beta-receptor (PDGF-beta-R) in pressure-induced ERK1/2 activation in intact rat mesenteric small arteries. In an organ culture model, vessels were pressurized (70 mm Hg) for 1 hour plus a 5-minute intervention period.

Small artery remodeling in hypertension.

Hypertension is associated with altered structure of the resistance vessels, a process known as remodeling. This review summarizes current concepts concerning the structure of a subgroup of the resistance vessels, the small arteries, and the modes of remodeling, some of the determinants of remodeling, and some signaling pathways for remodeling. It is shown that the available evidence points to important roles for blood flow and growth factors, in addition to blood pressure, as causes of resistance artery remodeling.