Hypertension and Angiogenesis

Abstract

Arterial Hypertension (AH) is characterized by reduced nitric oxide (NO) biosynthesis, activation of the Renin-Angiotensin-Aldosteron-System (RAAS), vasoconstriction, and microvascular rarefaction. The latter contributes to target organ damage, especially in left ventricular hypertrophy, and may partially be due to impaired angiogenesis. Angiogenesis, the formation of new microvessels and microvascular networks from existing ones, is a highly regulated process that arises in response to hypoxia and other stimuli and that relieves tissue ischemia. In AH, angiogenesis seems impaired. However, blood pressure alone does not affect angiogenesis, and microvascular rarefaction is present in normotensive persons with a family history for AH. Normal or increased NO in several processes and diseases enables or enhances angiogenesis (e.g. in portal hypertension) and reduced NO biosynthesis (for example, in a rat model of AH, in other disease models in vivo, and in endothelial NO Synthase knock out mice) impairs angiogenesis. Angiogenic growth factors such as Vascular Endothelial Growth Factor (VEGF) and Fibroblast Growth Factor (FGF) induce NO and require NO to elicit an effect. Effector molecules and corresponding receptors of the RAAS either induce (Bradykinin, Angiotensin II) or perhaps inhibit angiogenesis. The pattern of Bradykinin- and Angiotensin II-receptor expression and the capacity to normalize NO biosynthesis may determine whether ACE-inhibitors, Angiotensin II-receptor antagonists and other substances affect angiogenesis. Reconstitution of a normally vascularized tissue by reversal of impaired angiogenesis with drugs such as ACE inhibitors and AT1 receptor antagonists may contribute to successful treatment of hypertension-associated target organ damage, e.g. left ventricular hypertrophy.

Posterior reversible encephalopathy syndrome (PRES) after bevacizumab therapy for metastatic colorectal cancer

“…Hypertension is the most common side effect, and the proposed mechanism is a decrease in the release of nitric oxide from endothelial cells as a result of VEGF inhibition [5]. The incidence of hypertension varies from 16–38% [6]; however, the incidence of grade 3 or 4 hypertension is 16–18% and is dose-dependent [7].…”

Arterial stiffness in hypertensives in relation to expression of angiopoietin-1 and 2 genes in peripheral monocytes

“…5 Moreover, abnormal indices of angiogenesis in hypertension are correlated with target organ damage 6 and cardiovascular outcome. 4,7,8 The elevated Ang levels in hypertension suggest the possibility of alterations in the whole vessel remodelling process. 24 Given that angiogenesis plays a pivotal role in cardiovascular remodelling that may alter the mechanical wall properties, we sought a correlation between arterial stiffening, as expressed by pwv, and Ang-1 and Ang-2 gene expression in peripheral monocytes in patients with essential hypertension.…”

“…4 In particular, hypertensive patients exhibit higher levels of plasma angiopoietin-1 (Ang-1) and Ang-2, 5 which are correlated with target organ damage 6 and cardiovascular outcome. 4,7,8 Although Angs may exert a potent mitogenic effect and promote arterial remodelling, 9 the underlying pathophysiological mechanisms potentially linking angiogenesis with adverse outcome in hypertension are largely unclear.…”

Regular Endurance Exercise Decreases Blood Pressure via Enhancement of Angiogenesis and VEGF Expression in Spontaneously Hypertensive Rats

“…고혈압의 전형적인 특징인 말초저항의 증가는 비정상적인 말초조직의 미세혈관망의 분포와 밀접한 관련이 있고 [2,15,19], 이에 대한 실험적 증거도 고혈압환자 [15,16]와 고혈 압동물 [14,16,34]에서 모두 보고되었다. 중요한 것은 본태성고 혈압은 말초조직의 미세혈관분포가 감소되어 있고, 이것이 혈 압을 증가시키는 원인이라는 점이다 [27].…”

“…특히 본태성 고혈압은 원인이 명확하게 밝혀지지 않은 복잡 한 심혈관계질환으로 알려져 있지만, 선행연구들 [15,19]에 의 하면 혈관수축력의 증가와 혈관이완의 감소, 혈관의 구조적 변화, 그리고 비정상적인 미세혈관망(microvascular networks) 등을 그 특징으로 한다.…”