Angiogenesis and hypertension.

BACKGROUND: The formation of new blood vessels is an important process in embryonic development and in physiological repair processes. Abnormalities in blood vessel growth have been associated with various pathologies. HYPERTENSION AND IMPAIRED VASCULAR GROWTH: The basic observation underlying the hypothesis that essential hypertension is based on an impaired capacity for vascular growth is the nature of the structural alterations of microvascular beds in essential hypertension. Recent advances in understanding the molecular and cellular mechanisms of vascular growth suggest that the remodeling of individual vessels and vascular networks in hypertension may be a pathological variant of the formation of mature networks. PATHOGENESIS OF IMPAIRED VASCULAR GROWTH: Genetic and fetal influences appear to have significant effects in determining impaired vascular development as an early cause of essential hypertension.

The role of angiotensin II and prostaglandins in arcade formation in a developing microvascular network.

There are basically two types of branching patterns in the terminal part of the arteriolar tree. On the one hand, in a number of tissues, including the developing chick embryo chorioallantoic membrane (CAM), the pattern is dichotomous, whereas in other tissues many arteriolar-arteriolar connections, arcades, are found. The structure of the branching pattern depends on the local physical and chemical environment. The goal of this study was to investigate whether substances with an effect on vascular growth influence the vascular branching pattern. We treated chick embryo CAMs daily from day 7 to day 14 postfertilization with 0.9% NaCl, angiotensin II (ANG-II), ANG-II in combination with different angiotensin receptor subtype antagonists, i.e., losartan and CGP 42112A, or the prostaglandin synthesis inhibitor acetylsalicylic acid (ASA). Arcade formation was quantified by counting the number of arcades per cm2 treated area, the branch-node ratio and mean surface area of arcade loops. ANG-II caused a 2-fold increase in the number of arcades versus 0.9% NaCl. Addition of ASA or losartan caused a further enhancement of arcade formation expressed in the number and branch-node ratio. CGP 42112A had no significant effect on arcade formation. From these data we hypothesize that ANG-II stimulates the process of capillary upgrading to arterioles by stimulation of arteriolar smooth muscle cell growth. Prostaglandins normally counteract this effect. After blockade of prostaglandin action, the ANG-II-induced arterialization is enhanced, resulting in pronounced arcade formation. The actions of losartan may be related to its inhibitory effects on prostaglandins rather than angiotensin receptor antagonism.

Shear stress is not sufficient to control growth of vascular networks: a model study.

Local vessel wall shear stress is considered to be important for vessel growth. This study is a theoretical investigation of how this mechanism contributes to the structure of a vascular network. The analyses and simulations were performed on vascular networks of increasing complexity, ranging from single-vessel resistance to large hexagonal networks. These networks were perfused by constant-flow sources, constant-pressure sources, or pressure sources with internal resistances. The mathematical foundation of the local endothelial shear stress and vessel wall adaptation was as follows: delta d/delta t = K*(tau-tau desired)*d, where d is vessel diameter, tau desired is desired shear stress, and K is a growth factor. Single vessels and networks with vessels in series developed stable optimal diameters when perfused at constant flow or with a constant-pressure source with internal resistance. However, when constant-pressure perfusion was applied, these vessels developed ever-increasing diameters or completely regressed. In networks with two vessels in parallel, only one; vessel attained an optimal diameter and the other regressed, irrespective of the nature of the perfusion source. Finally, large hexagonal networks regressed to a single vessel when perfused with a pressure source with internal resistance. The behavior was independent of variation in parameters, although the adaptation rate and the diameter of the final vessel were altered. Similar conclusions hold for models of vascular trees. We conclude that the effect of shear stress on vascular diameter alone does not lead to stable network structures, and additional factor(s) must be present.