Synectin/syndecan-4 regulate coronary arteriolar growth during development.

Syndecan-4 and its cytoplasmic binding partner, synectin, are known to play a role in FGF-2 signaling and vascular growth. To determine their roles in coronary artery/arteriolar formation and growth, we compared syndecan-4 and synectin null mice with their wild-type counterparts. Image analysis of arterioles visualized by smooth muscle alpha-actin immunostaining revealed that synectin (-/-) mice had lower arteriolar length and volume densities than wild-type mice. As shown by electron microscopic analysis, arterioles from the two did not differ in morphology, including their endothelial cell junctions, and the organization and distribution of smooth muscle. Using micro-computer tomography, we found that the size and branching patterns of coronary arteries (diameters > 50 microm) were similar for the two groups, a finding that indicates that the growth of arteries is not influenced by a loss of synectin. Syndecan-4 null male mice also had lower arteriolar length densities than their gender wild-type controls. However, female syndecan-4 null mice were characterized by higher arteriolar length and volume densities than their gender-matched wild-type controls. Thus, we conclude that both synectin and syndecan-4 play a role in arteriolar development, a finding that is consistent with previous evidence that FGF-2 plays a role in coronary arterial growth. Moreover, our data reveal that gender influences the arteriolar growth response to syndecan-4 but not to synectin.     

Regression of ventricular hypertrophy abolishes cardiocyte vulnerability to acute hypoxia

Left ventricular hypertrophy (LVH) secondary to a pressure overload commonly leads to perfusion abnormalities that may limit oxygen delivery to the myocardium and, therefore, result in cardiocyte intracellular damage. We initiated this study to test the hypothesis that the increased vulnerability of the hypertrophied left ventricle to acute hypoxia is minimized when LVH regresses and maximal coronary flow returns to normal. Six-month-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were divided into control or one of two antihypertensive treatment groups. A 3-month treatment consisted of captopril (75-100 mg/kg) or hydralazine (80-160 mg/L) with hydrochlorothiazide (500 mg/L) added to each therapy. At the conclusion of the treatment period, the rats were administered a 7% O2-93% N2 gas mixture for 20 minutes to induce acute hypoxic stress during which time hemodynamics, blood gases, and pH were monitored. The heart was then rapidly fixed by vascular perfusion and prepared for electron microscopy. Captopril and hydralazine were equally effective in lowering arterial pressure in both strains, but only captopril was efficacious in reducing heart mass. Hypoxia-induced changes in hemodynamics, blood gases, and pH were similar in all of the groups; PO2 was decreased by about 70%. The electron micrographs revealed that the hypertrophied left ventricle consistently showed morphologic evidence of hypoxic damage (as indicated by T-tubular swelling, intracellular edema, and mitochondrial alterations); in contrast hypoxia had little effect on the non-hypertrophied ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of maternal cadmium exposure on postnatal development and tissue cadmium,copper and zinc concentrations in rats

Administration of 60 ppm cadmium (Cd) in drinking water from the 1^st to the 20^th day of gestation to female rats did not affect the viability, body weight gain, food, and water consumption of offspring. The blood hemoglobin level was reduced in 2-week-old females and males but not in 16-week-old offspring. Hematocrit and serum glucose level were not affected at either age. Cadmium concentration in the intestinal wall was increased in both age groups, with marginal uptake in other organs. A decrease in copper (Cu) concentration was found in the brain of 2-week-old offspring of both sexes and of 16-week-old females. The brain zinc (Zn) concentration was decreased only in 16-week-old animals. The physical and neuromuscular development of offspring before weaning was not impaired by maternal Cd treatment. The alterations in Cu and Zn metabolism were associated with reduced locomotor activity and affected open-field behavior in adult offspring of either sex and with decreased avoidance acquisition in adult female offspring.The results obtained suggest a relationship between the reduced brain Cu and Zn levels and CNS dysfunction in adult offspring of female rats exposed to Cd during gestation.     

MR spectroscopy using multi-ring surface coils.

A spatially uniform B(1)-field is preferred for MR imaging and spectroscopy. Unfortunately, volume coils are sometimes unavailable, or do not provide adequate RF power or SNR for some applications. In quantitative MRS, mean metabolite concentration cannot be evaluated when the coil response is nonuniform, unless an assumption is made concerning the metabolite spatial distribution. It is well known that standard single-loop surface coils, although offering high SNR characteristics, have poor B(1) homogeneity. New multi-ring surface coils are proposed which produce a locally uniform B(1) field, with sensitivity and power requirements comparable to those of standard surface coils. MR spectroscopy using two and three-ring versions of this "local volume coil" result in spatial localization essentially identical to that obtained with a volume coil but with much improved RF power and SNR characteristics. When compared to standard surface coils, the multi-ring coil offers much improved water suppression and localization, as well as reduced outer voxel contamination, with only a small loss in SNR and moderate increase in SAR. In summary, the multi-ring coil operates midway between the volume coil and the standard surface coil, retaining the most advantageous properties of both. Magn Reson Med 42:655-664, 1999. Published 1999 Wiley-Liss, Inc.