Cardiac microvascular changes in DOCA-salt hypertensive rats: effect of endothelin ETA receptor antagonism

Larouche, Isabelle; Schiffrin, Ernesto L.

doi:10.1016/s0895-7061(99)80009-0

Cited by 8 publications

(11 citation statements)

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“…The dilated cardiomypathic hamster heart exhibited a decrease in proportion of venular capillaries with a reduction of total capillary density (29), and an increase in arteriolar capillaries with the decrease in capillary density in the heart was observed in hypertensive rats with cardiac hypertrophy (31). Also further deterioration of these pathological cardiac diseases was associated with the reduction of total capillary density and an alteration in the proportion of venular and arteriolar capillaries in the heart.…”

Section: Discussionmentioning

confidence: 95%

Exercise training improves aging-induced downregulation of VEGF angiogenic signaling cascade in hearts

Iemitsu¹,

Maeda²,

Jesmin³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

116

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Exercise training improves aging-induced deterioration of angiogenesis in the heart. However, the mechanisms underlying exercise-induced improvement of capillary density in the aged heart are unclear. Vascular endothelial growth factor (VEGF) is implicated in angiogenesis, which activated angiogenic signaling cascade through Akt and endothelial nitric oxide synthase (eNOS)-related pathway. We hypothesized that VEGF angiogenic signaling cascade in the heart contributes to a molecular mechanism of exercise training-induced improvement of capillary density in old age. With the use of hearts of sedentary young rats (4 mo old), sedentary aged rats (23 mo old), and exercise-trained aged rats (23 mo old, swim training for 8 wk), the present study investigated whether VEGF and VEGF-related angiogenic molecular expression in the aged heart is affected by exercise training. Total capillary density in the heart was significantly lower in the sedentary aged rats compared with the sedentary young rats, whereas that in the exercise-trained rat was significantly higher than the sedentary aged rats. The mRNA and protein expressions of VEGF and of fms-like tyrosine kinase-1 (Flt-1) and fetal liver kinase-1 (Flk-1), which are main VEGF receptors, in the heart were significantly lower in the sedentary aged rats compared with the sedentary young rats, whereas those in the exercise-trained rats were significantly higher than those in the sedentary aged rats. The phosphorylation of Akt protein and eNOS protein in the heart corresponded to the changes in the VEGF protein levels. These findings suggest that exercise training improves aging-induced downregulation of cardiac VEGF angiogenic signaling cascade, thereby contributing to the exercise training-induced improvement of angiogenesis in old age.

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Section: Discussionmentioning

confidence: 95%

Exercise training improves aging-induced downregulation of VEGF angiogenic signaling cascade in hearts

Iemitsu¹,

Maeda²,

Jesmin³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

116

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“…In normotensive rats, chronic administration of ET A R antagonist does not affect blood pressure, suggesting that ET may not be involved in the regulation of normal blood pressure [75]. Also, some studies have shown that chronic treatment with the ET A R antagonist A127722 or BQ123 only slightly lowers blood pressure in SHR and DOCA-salt hypertensive rats, and has no effect in renovascular model of HTN, suggesting that ET plays little role in these forms of HTN [57,76]. Other studies have shown that acute administration of the selective ET A R antagonist ABT-627 markedly decreases blood pressure in DOCA-salt rats, and chronic treatment with ABT-627 suppresses the development of HTN [74].…”

Section: Et Receptor Antagonists and Management Of Htnmentioning

confidence: 99%

Modulators of the Vascular Endothelin Receptor in Blood Pressure Regulation and Hypertension

Khalil¹

2011

CMP

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Endothelin (ET) is one of the most investigated molecules in vascular biology. Since its discovery two decades ago, several ET isoforms, receptors, signaling pathways, agonists and antagonists have been identified. ET functions as a potent endothelium-derived vasoconstrictor, but could also play a role in vascular relaxation. In endothelial cells, preproET and big ET are cleaved by ET converting enzymes into ET-1, −2, −3 and −4. These ET isoforms bind with different affinities to ETA and ETB receptors in vascular smooth muscle (VSM), and in turn increase [Ca2+]i, protein kinase C and mitogen-activated protein kinase and other signaling pathways of VSM contraction and cell proliferation. ET also binds to endothelial ETB receptors and stimulates the release of nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor. ET, via endothelial ETB receptor, could also promote ET re-uptake and clearance. While the effects of ET on vascular reactivity and growth have been thoroughly examined, its role in the regulation of blood pressure and the pathogenesis of hypertension is not clearly established. Elevated plasma and vascular tissue levels of ET have been identified in salt-sensitive hypertension and in moderate to severe hypertension, and ET receptor antagonists have been shown to reduce blood pressure to variable extents in these forms of hypertension. The development of new pharmacological and genetic tools could lead to more effective and specific modulators of the vascular ET system for treatment of hypertension and related cardiovascular disease.

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“…Again, the local renin-angiotensin-aldosterone system seems to play a dominant role, with angiotensin II and aldosterone as mediators [5,38]. Endothelial factors may also have a significant role [45]. We recently studied the effect of long-term angiotensin II type 1 receptor blockade with candesartan on cardiovascular mass and systemic and coronary circulation in adult SHR (unpublished observations).…”

Section: Ventricular Fibrosis In Hypertensive Left Ventricular Hypertmentioning

confidence: 99%

Hypertension and the heart

Sušić

Fröhlich

2000

Curr Hypertens Rep

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Sustained increase in arterial pressure causes left ventricular hypertrophy and adversely affects all myocardial compartments: myocytes, interstitium, and coronary vasculature. Ventricular hypertrophy significantly increases the risk for cardiovascular morbidity and mortality in hypertensive disease. Impairments in coronary circulation and ventricular fibrosis, which are an essential part of hypertensive disease, contribute to that increased risk. This report discusses the mechanisms of hypertension-induced myocardial collagen accumulation and impairments in coronary hemodynamics. Particular attention is given to the interaction of hypertension and aging because aging aggravates hypertensive changes and the incidence of hypertension increases with aging. The effect of therapy on hypertension-induced ventricular fibrosis and impairment in coronary hemodynamics and the risk associated with these changes are also discussed.

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Cardiac microvascular changes in DOCA-salt hypertensive rats: effect of endothelin ETA receptor antagonism

Cited by 8 publications

References 0 publications

Exercise training improves aging-induced downregulation of VEGF angiogenic signaling cascade in hearts

Exercise training improves aging-induced downregulation of VEGF angiogenic signaling cascade in hearts

Modulators of the Vascular Endothelin Receptor in Blood Pressure Regulation and Hypertension

Hypertension and the heart

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