The content and fatty acyl composition of phospholipids were examined in pressure-overload hypertrophied hearts. Cardiac hypertrophy was induced in rats by abdominal aortic constriction. Twenty-one days postconstriction the content of myocardial phosphatidylcholine (PC), sphingomyelin, and phosphatidylinositol (PI) was significantly elevated by 10, 10, and 20%, respectively. The essential fatty acid, linoleic acid, was markedly reduced in PC, phosphatidylethanolamine (PE), PI, and cardiolipin (CL) of hypertrophied hearts. The associated changes in fatty acyl composition were specific for the individual phospholipid class as evidenced by a significant elevation of palmitic acid in PC, docosahexaenoic acid in PE and oleic acid in CL. Alterations in fatty acyl composition of phospholipids were associated with no change in the composition of cardiac triglycerides, cardiac free fatty acids or serum lipids. The fatty acyl composition of phospholipids was also altered in pressure-overload hypertrophied hearts of cats, as evidenced by a reduction of linoleic acid and an elevation of arachidonic acid in total phospholipids. These findings demonstrate that changes in phospholipid metabolism occur in the pressure-overloaded mammalian heart. Such alterations may contribute to altered membrane function in the hypertrophied myocardium.

A precise description of the involvement of G proteins in regulation of the cardiovascular system is not possible at the present time although it is clear that they do have important regulatory roles. The cardiovascular system is composed of a variety of cell types, which are subject to control by several different hormones, as well as by hormones that have several different effects in the same cell type. Although, historically, variations in the type and number of receptors located on each cell have been used to explain this diversity of hormonal responses, we must now consider the large number and diversity of G proteins in any effort to understand the coordinated hormonal regulation of cellular functions. Given that there are eight known G proteins and several others have been speculated, each of which is composed of three subunits, each of which has several different forms, the possible combinations of subunits into functionally distinct G proteins is enormous. To place this newly described family of G proteins into the appropriate hormone signaling pathways will require a continued research effort. However, with recent progress in producing specific antibodies to each of the G protein subunits, it may now be possible to determine the specific receptor-effector functions of each G protein and their individual subunits.

The toxicity of a series of 120 aliphatic alcohols was evaluated using the Tetrahymena pyriformis population growth impairment assay. For tertiary propargylic alcohols; primary, secondary, and tertiary homopropargylic alcohols; allylic alcohols; and saturated alcohols, a statistically robust structure-activity model was developed for toxicity data [log (IGC(50) (-1))] using the 1-octanol/water partition coefficient (log K(ow)) as the lone descriptor [log (IGC(50))(-1) = 0.74 (log K(ow)) - 1.73; n = 97; r(2) (adj.) = 0.933; r(2) (pred.) = 0.932; s = 0.298; F = 1328; Pr > F = 0.0001]. Analysis of data for the primary propargylic alcohols yielded a separate, high-quality log K(ow)-dependent quantitative structure-activity relationship (QSAR) [log (IGC(50))(-1) = 0.65 (log K(ow)) - 1.22; n = 10; r(2) (adj.) = 0.969; r(2) (pred.) = 0.964; s = 0.222; F = 254; Pr > F = 0.0001]. A comparison of the observed toxicity and that predicted by the first QSAR showed that the primary propargylic alcohols with log K(ow) values < 2.00 exhibited enhanced toxicity and that this increased toxicity was inversely related to hydrophobicity. In sharp contrast, analysis of the data for the secondary propargylic alcohols exhibited little relationship with log K(ow) (r(2) = 0.339). Although the initial QSAR can be used to model the toxicity of any aliphatic alcohol for the T. pyriformis population growth impairment end point, the estimated potency would be underestimated for primary propargylic alcohols with log K(ow) values < 2.00. Moreover, estimates of toxic potency of secondary propargylic alcohols based on this QSAR should be viewed with limited confidence. The findings for beta-unsaturated alcohols in Tetrahymena were sharply different from that reported for fathead minnow acute mortality; this difference in toxicity is a result of a difference in the protocol used rather than in metabolism.

As a first step in understanding the functioning of hormonal signaling pathways in the heart, the G protein composition of neonatal and adult rat hearts was determined by immunoblotting analysis. Neonatal rat cardiac myocytes and nonmuscle heart cells contained Gs alpha 52, Gi alpha 1,3, and Gi alpha 2 with little or no Gs alpha 45 or Go alpha 39. Interestingly, Go alpha 39 accumulated fourfold in cardiac myocytes between days 1 and 6 of culture. Atrial membranes from adult rat hearts had approximately equal amounts of the 45- and 52-kDa forms of Gs alpha, whereas adult ventricles had predominantly Gs alpha 45. In addition, adult atria contained relatively more Gi alpha 1,3, Gi alpha 2, and Go alpha 39 than adult ventricle. Moreover, the increase in Go alpha 39 observed in cardiac myocytes cultured for 6 days could be prevented by culturing cells in medium containing 50 mM KCl. The observed differences in G protein expression between cell types and between contracting and KCl-depolarized cardiac myocytes may provide a system to investigate the function of various G proteins and to study regulation of their expression.

No abstract