Internal mammary artery grafts reactivity in hypertensive patients: role of stretching in extraendothelial nitric oxide.

BACKGROUND: The internal mammary artery (IMA) used in bypass coronary surgery remains efficient for a longer time than other grafts, such as saphenous veins; however, its biological characteristics are incompletely defined. OBJECTIVE: To compare in IMA grafts from hypertensive (HT) and normotensive (NT) patients the presence of endothelium and their functionability, the response to passive stretching and basal tone, the reactivity to exogenous vasoconstrictors, the role of stretching in NO release, and the possible extraendothelial NO source. METHODS AND RESULTS: IMA rings contractility, presence of endothelium, and nitrite release were studied. An endothelial dysfunction associated with hypertension was found. IMA rings from HT had an impaired response to passive stretching, resulting in a decreased relaxation. All IMA grafts had an increased basal tone demonstrated by relaxation to SNP; however, a lesser response was found in HT. Interestingly, it was demonstrated that NO release was present in IMA grafts, despite an endothelial dysfunction and that stretching increased NO release. This effect was inhibited by Ca2+ -free media, L-NAME and a specific neuronal NO synthase (nNOS) inhibitor. Furthermore, the demonstration of the presence of nNOS in smooth muscle cells by immunohistochemistry supports a role of extraendothelial NO. CONCLUSION: We demonstrate the impact of hypertension in IMA grafts producing increased endothelial dysfunction, reduced response to passive stretching, increased basal tone, and impaired responsiveness to exogenous vasoconstrictors and NO release. A specific role of stretching in extraendothelial NO release was demonstrated, which may have an important role in the outcome of IMA grafts due to the protective actions of NO, even in the absence of the endothelium.

Structural changes in the renal vasculature in streptozotocin-induced diabetic rats without hypertension.

BACKGROUND/AIM: We evaluated in diabetic-streptozotocin rats (STZR) the structural changes of glomeruli, preglomerular vessels, glomerular tuft and renal parenchyma in order to determine the degree of renal injury and the presence of remodeling in afferent arterioles developed by diabetes without overimposed hypertension. METHODS: Renal mass index and histological score (glomerular number, density, tubular lesions and degree of arteriosclerosis) were estimated. In afferent arterioles the ratio of wall thickness/lumen was obtained by stereological methods. RESULTS: STZR developed diabetes without hypertension; renal mass index increased and matched changes in glomeruli (decrease of capillary number and enlargement of mesangium and basement capillary membrane). Both glomerular number and density as well as afferent arteriole number were diminished. Degenerative changes in both proximal (glycogenic and hyaline degeneration) and distal tubules (hyaline casts) were also observed. At variance with preglomerular vessels, the efferent arterioles only presented initial arteriosclerosis. Finally, the stereological study of afferent arterioles showed a significantly lower arteriolar lumen area and arteriolar wall thickness in STZR, resulting in a remodeling without modification of wall/lumen ratio. CONCLUSION: Diabetes, uncomplicated by hypertension, is associated with (1) a reduction in glomerular number; (2) degeneration in parenchyma and renal tubules, and (3) a specific pattern of remodeling in preglomerular vessels different from that induced by hypertension. Although this work demonstrated that these changes are not triggered by hypertension, further investigations are required in order to determine which mediators are involved in diabetic-vascular renal dysfunction.