Angiotensin II (Ang II) is a potent vasopressor peptide that interacts with 2 major receptor isoforms -AT1 and AT2. Although blood pressure is increased in AT2 knockout mice, the underlying mechanisms remain undefined because of the low levels of expression of AT2 in the vasculature. Here we overexpressed AT2 in vascular smooth muscle (VSM) cells in transgenic (TG) mice. Aortic AT1 was not affected by overexpression of AT2. Chronic infusion of Ang II into AT2-TG mice completely abolished the AT1-mediated pressor effect, which was blocked by inhibitors of bradykinin type 2 receptor (icatibant) and nitric oxide (NO) synthase (L-NAME). Aortic explants from TG mice showed greatly increased cGMP production and diminished Ang II-induced vascular constriction. Removal of endothelium or treatment with icatibant and L-NAME abolished these AT2-mediated effects. AT2 blocked the amiloride-sensitive Na + /H + exchanger, promoting intracellular acidosis in VSM cells and activating kininogenases. The resulting enhancement of aortic kinin formation in TG mice was not affected by removal of endothelium. Our results suggest that AT2 in aortic VSM cells stimulates the production of bradykinin, which stimulates the NO/cGMP system in a paracrine manner to promote vasodilation. Selective stimulation of AT2 in the presence of AT1 antagonists is predicted to have a beneficial clinical effect in controlling blood pressure.

Background-Helicobacter pyloni is a

To examine the efficacy of Lactobacillus gasseri OLL2716 (LG21) as a probiotic for Helicobacter pylori in humans, 31 subjects infected with the bacterium ingested yogurt containing LG21 daily for an 8 week period. The [(13)C]urea breath test and assays of serum pepsinogens revealed a significant improvement following LG21 treatment. LG21 was thus determined to be effective in both suppressing H. pylori and reducing gastric mucosal inflammation.

Myocardial stiffening may be attributed to progressive collagen accumulation, collagen phenotype shift and enhanced collagen cross-linking, but not to either compensatory LV hypertrophy or LV hypertrophy that progresses from the compensatory stage.

Background-Matrix metalloproteinases (MMPs) are activated in dilated failing hearts, and angiotensin-converting enzyme (ACE) inhibition prevents left ventricular (LV) dilatation. However, it remains unclear whether activation of MMPs precedes or is secondary to LV remodeling, and an effect of ACE inhibition on MMPs is unknown. Methods and Results-Dahl salt-sensitive rats fed a high-salt diet from 8 weeks served as the hypertensive heart failure (HF) model. LV echo, histological study, measurement of mRNA levels, and gelatin zymography were performed before (at 23 weeks) and after (at 26 weeks) the development of LV dilatation and pulmonary edema. The same procedures were conducted in the HF model rats treated with a subdepressor dose of ACE inhibitor (enalapril 5 mg · kg Ϫ1 · d