Effects of total replacement of atrial myosin light chain-2 with the ventricular isoform in atrial myocytes of transgenic mice.

Background: In contrast to their well-known and critical role in excitation-contraction coupling of vascular smooth muscle, the effects of the myosin light chains on cardiomyocyte mechanics are poorly understood. Accordingly, we designed the present experiment to define the cardiac chamber-specific functional effects of the ventricular isoform of the regulatory myosin light chain (MLC2v).

Methods And Results: Postnatal transgenic cardiac-specific overexpression of MLC2v was achieved by use of the alpha-myosin heavy chain promoter.

Left atrial systolic and diastolic function after cessation of pacing in tachycardia-induced heart failure.

Studies in the rapid-pacing model of heart failure have shown that left ventricular (LV) systolic function normalizes on cessation of pacing and LV diastolic dysfunction persists, but there is no information regarding atrial function under these conditions. To determine the effects of cessation of pacing on left atrial (LA) systolic and diastolic function, ten dogs with rapid pacing-induced heart failure (250 beats/min for 3-4 wk), six dogs with regression of heart failure (4 wk after cessation of rapid pacing), and seven control dogs were instrumented with LA sonomicrometers and micromanometers. At matched LA pressure, LA ejection (10.

The effects of a thyroid hormone analog on left ventricular performance and contractile and calcium cycling proteins in the baboon.

To determine the biochemical and related functional effects of the thyroid analog diiodothyroproprionic acid (DITPA) on primate myocardium, we examined, both before and after 23 days of DITPA (3.75 mg/kg): myosin heavy-chain (MHC) isoforms and sarcoplasmic reticulum (SR) calcium cycling proteins; left ventricular (LV) function; and the LV force-frequency relation in four baboons chronically instrumented with sonomicrometers and micromanometers. The force-frequency relation was measured as the response of isovolumic contraction (dP/dtmax) to incremental pacing and the critical heart rate (HRcrit) as the rate at which dP/dtmax reached its maximum.

In vivo determination of left ventricular wall stress-shortening relationship in normal mice.

Although targeted alterations of the mouse genome are used increasingly to identify the mechanisms underlying cardiac function, the methods used to study the phenotypic expression of these alterations in vivo are limited. To derive a relatively noninvasive, load-independent measure of left ventricular (LV) contractility in mice, we cannulated the femoral artery and performed two-dimensional directed M-mode echo studies in 28 anesthetized FVB/N mice, using a 9-MHz transducer. Loading conditions were altered by intraarterial methoxamine (3-12 microg/g), and LV shortening fraction was determined at several steady states, both before and after myocardial contractility was altered by either 4 microg/g intraperitoneal dobutamine (n = 16) or 1-2 microg/g verapamil (n = 12).

Effects of thyroid hormone on left ventricular performance and regulation of contractile and Ca(2+)-cycling proteins in the baboon. Implications for the force-frequency and relaxation-frequency relationships.

The transcriptional, posttranscriptional, and related functional effects of thyroid hormone on primate myocardium are poorly understood. Therefore, we studied the effects of thyroid hormone on sarcoplasmic reticulum (SR) Ca(2+)-cycling proteins and myosin heavy chain (MHC) composition at the steady state mRNA and protein level and associated alterations of left ventricular (LV) performance in 8 chronically instrumented baboons. The force-frequency and relaxation-frequency relations were assessed as the response of LV isovolumic contraction (dP/dtmax) and relaxation (Tau), respectively, to incremental atrial pacing.

The role of the cytoskeleton in left ventricular pressure overload hypertrophy and failure.

To characterize alterations in gene expression which may occur during the development of compensated left ventricular pressure overload hypertrophy (CH) and the transition to decompensated congestive heart failure (DH), differential RNA display was used to compare mRNA transcripts from sham operated, 4-week, and 8-week thoracic aorta banded guinea-pigs. Of several regulated transcripts chosen for analysis, one was identified by nucleotide sequence homology as titin, a sarcomeric cytoskeletal protein. By differential display and comparative PCR, titin transcripts were increased in CH and then declined in DH.

Increased dietary salt sensitizes vasomotor neurons of the rostral ventrolateral medulla.

Excess dietary sodium is a major contributing factor to the incidence and severity of hypertension. However, the precise mechanism or mechanisms by which salt contributes to the severity of hypertension are unknown. The region of the rostral ventrolateral medulla (RVLM) is a principal brain stem locus critical for the regulation of arterial blood pressure by the sympathetic nervous system.

Evidence for a kynurenate-insensitive glutamate receptor in nucleus tractus solitarii.

Previous studies have shown that pharmacological blockade of ionotropic excitatory amino acid (EAA) receptors in the nucleus tractus solitarii (NTS) with kynurenate (Kyn) abolishes baroreceptor reflexes but fails to affect cardiovascular responses evoked by microinjections of L-glutamate (Glu) into the NTS. These observations have raised doubts as to whether Glu is a neurotransmitter of baroreceptor information in the NTS because the pharmacological actions of exogenously administered Glu are not identical to those of the neurotransmitter released in the NTS coincident with baroreceptor activation. One possible explanation for these results is that exogenously administered Glu might act at receptors that are not blocked by Kyn and are not accessible to synaptically released Glu in the NTS baroreflex pathway.