This review highlights recent findings about the role that endothelial glycocalyx and caveolae play in vascular homeostasis. We describe the structure, synthesis, and function of glycocalyx and caveolae in vascular cells under physiological and pathophysiological conditions. Special focus will be given in glycocalyx and caveolae that are associated with impaired production of nitric oxide (NO) and generation of reactive oxygen species (ROS). Such alterations could contribute to the development of cardiovascular diseases, such as atherosclerosis, and hypertension.

Nitrate and nitrite supplement deficient endogenous nitric oxide (NO) formation. While these anions may generate NO, recent studies have shown that circulating nitrite levels do not necessarily correlate with the antihypertensive effect of oral nitrite administration and that formation of nitrosylated species (RXNO) in the stomach is critically involved in this effect. This study examined the possibility that RXNO formed in the stomach after oral nitrite administration promotes target protein nitrosylation in the vasculature, inhibits vasoconstriction and the hypertensive responses to angiotensin II. Our results show that oral nitrite treatment enhances circulating RXNO concentrations (measured by ozone-based chemiluminescence methods), increases aortic protein kinase C (PKC) nitrosylation (measured by resin-assisted capture SNO-RAC method), and reduces both angiotensin II-induced vasoconstriction (isolated aortic ring preparation) and hypertensive ( in vivo invasive blood pressure measurements) effects implicating PKC nitrosylation as a key mechanism for the responses to oral nitrite. Treatment of rats with the nitrosylating compound S-nitrosoglutathione (GSNO) resulted in the same effects described for oral nitrite. Moreover, partial depletion of thiols with buthionine sulfoximine prevented PKC nitrosylation and the blood pressure effects of oral nitrite. Further confirming a role for PKC nitrosylation, preincubation of aortas with GSNO attenuated the responses to both angiotensin II and to a direct PKC activator, and this effect was attenuated by ascorbate (reverses GSNO-induced nitrosylation). GSNO-induced nitrosylation also inhibited the increases in Ca2+ mobilization in angiotensin II-stimulated HEK293T cells expressing angiotensin type 1 receptor. Together, these results are consistent with the idea that PKC nitrosylation in the vasculature may underlie oral nitrite treatment-induced reduction in the vascular and hypertensive responses to angiotensin II.

In this work, we hypothesized that cyclooxygenase (COX) activity can be regulated by nitric oxide (NO) and hydrogen peroxide (HO). In the renal hypertension (2K-1C), phenylephrine (PE)-induced contraction was lower than in normotensive (2K) rat aortas. This impaired contraction is due to NO/HO- induced vasodilation. We evaluated the effects of HO on the activity of COX and endothelial NO-Synthase (eNOS) in 2K-1C rat aortas stimulated with PE. Responses for PE or HO were evaluated in 2K-1C and 2K rat aortas, without or with inhibitors for COX (Indomethacin) or eNOS (L-NAME). COX isoforms expression was evaluated by Western blotting. eNOS inhibition was tested on thromboxane A (TXA) and prostacyclin (PGI) production. PE-induced contraction was lower in 2K-1C than in 2K. Indomethacin reduced PE-induced contraction in 2K, but it had no effect in 2K-1C. L-NAME reversed indomethacin-induced effect in 2K and it normalized PE-induced contraction in 2K-1C to the normotensive levels. COX-1 and COX-2 expression, TXA and PGI production were higher in 2K-1C than in 2K. eNOS inhibition did no modify TXA/PGI production. In low concentrations, HO induced relaxation only in 2K that was abolished by L-NAME while the contractions induced by high concentrations were abolished by indomethacin in both 2K and 2K-1C. The activity/expression of COX, and TXA/PGI production were increased in 2K-1C, which were not modified by eNOS. High levels of HO increased the endothelial COX activity, which induced contraction. Therefore, an high increase in HO production may increase COX-induced vasoconstriction rather than eNOS-induced relaxation, which might contribute to aggravate hypertension.

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