Low adherence was the most common cause of poor blood pressure control in patients with apparent resistant hypertension, being twice as frequent as secondary causes of hypertension. Incomplete adherence was far more common than complete nonadherence; thus, assessment of adherence in patients on multiple drug regime is only reliable when all drugs are included in assessment. Assessing adherence by toxicological urine screening is a useful tool in detecting low adherence, especially in the setting of multidrug regimen as a cause of apparently resistant hypertension.

The rational construction and operation of an ideal helical spring has been investigated. The infinite helices, [Ag(Py 2 O)]X (Py 2 O ) 3,3′-oxybispyridine; X -) NO 3 -, BF 4 -, ClO 4 -, and PF 6 -), have been constructed in high yield via cooperative effects of the skewed conformer of Py 2 O and the potential linear geometry of the N-Ag(I)-N bond. Crystallographic characterization reveals that the polymer framework is an ideal cationic cylindrical helix and that its counteranions are pinched in two columns inside the helix. The four anions have been exchanged for each other in an aqueous solution without destruction of the helical skeleton. In particular, [Ag(Py 2 O)]NO 3 prepared by the counteranion exchange can be isolated as crystals suitable for X-ray crystallography in water. The helical pitch is reversibly stretched via the counteranion exchange from 7.430(2) to 9.621(2) Å, and is exactly proportional to the volume of the anion guests. This pitch-tuning is attributed to subtle change in the nonrigid dihedral angles between two pyridyl groups around O and Ag atoms that act as hinges within the helical subunit. Thermal analyses indicate that the helical compounds are stable up to 231-332 °C in the solid state.

Abstract-The bioavailability of nitric oxide (NO) within the vascular wall is limited by superoxide anions (O 2 ·Ϫ ). The relevance of extracellular superoxide dismutase (ecSOD) for the detoxification of vascular O 2 ·Ϫ is unknown. We determined the involvement of ecSOD in the control of blood pressure and endothelium-dependent responses in angiotensin II-induced hypertension and renovascular hypertension induced by the two-kidney, one-clip model in wild-type mice and mice lacking the ecSOD gene. Blood pressure was identical in sham-operated ecSOD ϩ/ϩ and ecSOD Ϫ/Ϫ mice. After 6 days of angiotensin II-treatment and 2 and 4 weeks after renal artery clipping, blood pressure was significantly higher in ecSOD Ϫ/Ϫ than ecSOD ϩ/ϩ mice. Recombinant ecSOD selectively decreased blood pressure in hypertensive ecSOD Ϫ/Ϫ mice, whereas ecSOD had no effect in normotensive and hypertensive ecSOD ϩ/ϩ mice. Compared with sham-operated ecSOD ϩ/ϩ mice, sham-operated ecSOD Ϫ/Ϫ mice exhibited attenuated acetylcholineinduced relaxations. These responses were further depressed in vessels from clipped animals. Vascular O 2 ·Ϫ , as measured by lucigenin chemiluminescence, was higher in ecSOD Ϫ/Ϫ compared with ecSOD ϩ/ϩ mice and was increased by clipping. The antioxidant tiron normalized relaxations in vessels from sham-operated and clipped ecSOD Ϫ/Ϫ , as well as from clipped ecSOD ϩ/ϩ mice. In contrast, in vivo application of ecSOD selectively enhanced endothelium-dependent relaxation in vessels from ecSOD Ϫ/Ϫ mice. These data reveal that endogenous ecSOD is a major antagonistic principle to vascular O 2 ·Ϫ , controlling blood pressure and vascular function in angiotensin II-dependent models of hypertension. ecSOD is expressed in such an abundance that even in situations of high oxidative stress no relative lack of enzyme activity occurs.

Background-Isoforms of the NADPH oxidase contribute to vascular superoxide anion ( · O 2 Ϫ ) formation and limit NO bioavailability. We hypothesized that the endothelial gp91phox-containing NADPH oxidase is predominant in generating the O 2 Ϫ to scavenge endothelial NO and thus is responsible for the development of endothelial dysfunction. Methods and Results-Endothelial dysfunction was studied in aortic rings from wild-type (WT) and gp91phox-knockout (gp91phox Ϫ/Ϫ ) mice with and without renovascular hypertension induced by renal artery clipping (2K1C). Hypertension induced by 2K1C was more severe in WT than in gp91phox Ϫ/Ϫ mice (158Ϯ2 versus 149Ϯ2 mm Hg; PϽ0.05). Endothelium-dependent relaxation to acetylcholine (ACh) was attenuated in rings from clipped WT but not from clipped gp91phox Ϫ/Ϫ mice. The reactive oxygen species (ROS) scavenger Tiron, PEG-superoxide dismutase, and the NADPH oxidase inhibitory peptide gp91ds-tat enhanced ACh-induced relaxation in aortae of clipped WT mice. Inhibition of protein kinase C, Rac, and the epidermal growth factor receptor kinase, elements involved in the activation of the NADPH oxidase, restored normal endothelium-dependent relaxation in vessels from clipped WT mice but had no effect on relaxations in those from gp91phox Ϫ/Ϫ mice. Relaxations to exogenous NO were attenuated in vessels from clipped WT but not clipped gp91phox Ϫ/Ϫ mice. After removal of the endothelium or treatment with PEG-superoxide dismutase, NO-induced relaxations were identical in vessels from clipped and sham-operated WT and gp91phox mice. Conclusions-These data indicate that the formation of O 2Ϫ by the endothelial gp91phox-containing NADPH oxidase accounts for the reduced NO bioavailability in the 2K1C model and contributes to the development of renovascular hypertension and endothelial dysfunction.