Measuring high pressure baroreceptor sensitivity in the rat.

INTRODUCTION: The high pressure baroreceptor reflex rapidly buffers changes in systemic arterial pressure in response to postural changes, altered gravitational conditions, diseases, and pharmacological agents. Drug-induced exaggeration of changes in heart rate and in systemic arterial pressure is a leading cause of adverse events and of patients terminating use of drugs, particularly in the aging population. This paper presents a facile method for monitoring the high pressure baroreceptor reflex in rats, and presents an alternative to quantifying the magnitude of this reflex using 2 dependent variables, heart rate and systemic arterial pressure, rather than merely change in heart rate. METHODS: Twenty-four rats were allocated to 3 groups: group I anesthetized with 100mg/kg thiopental, group II anesthetized with 2% isoflurane given by inhalation, group III anesthetized with thiopental but pretreated for 2weeks with 2µg/kg aldosterone given SQ bid. After induction to anesthesia, hair was clipped from the ventral aspect of the neck, and petrolatum was applied to the skin to permit an air-tight seal with a glass funnel attached to a source of variable and controllable negative pressure. Systemic arterial pressure, ECG, heart rate, and a force of suction applied to the neck were all recorded continuously. RESULTS: After baseline recordings, a force of -20mmHg was applied for 20s over the carotid artery. In rats receiving thiopental, the average changes in heart rate and systemic arterial pressure following the application of -20mmHg neck suction were 30±11bpm and 45±14mmHg, respectively. The ratios of change in heart and change in systemic arterial pressure to application of negative force over the carotid sinus are 1.5±0.6bpm/mmHg and 0.7±04mmHg/mmHg, respectively. Mean values for heart rate and for mean systemic arterial pressure during baseline and after application of neck suction for 20s showed little to no decrease (i.e., blunting) in rats anesthetized with isoflurane or pretreated with aldosterone. DISCUSSION: Thus this methodology was able to detect, in rats, blunting of baroreceptor function for at least 2 perturbations of this important homeostatic control system.

Endurance training increases the expression of mitochondrial and nuclear encoded cytochrome c oxidase subunits and heat shock proteins in rat skeletal muscle.

Cytochrome c oxidase (CCO) is an enzyme complex found on the inner mitochondrial membrane and serves as the final electron acceptor in mitochondrial electron transport. Heat shock proteins (HSPs) are involved in the import of nuclear encoded protein subunits into the mitochondria and induce conformational changes to form active enzyme complexes. As both the nuclear and mitochondrial encoded subunits of CCO have been shown to increase in activity and expression in muscle subsequent to artificial loading, and as exercise has been shown to induce HSPs, we sought to determine whether 16-20 weeks of treadmill exercise would result in enhanced CCO subunit expression, and to determine if there was a relationship between this expression and HSP content in medial gastrocnemius muscle of Fischer 344 rats. Our results indicated that endurance training resulted in a 53%, 87% and 80% increase (P<0.05) in the levels of HSP 60, CCO subunit II and CCO subunit VI, respectively. Enzymatic activity of CCO was 84% greater (P<0.05) after endurance training. Mann Whitney U analyses showed that CCO subunit II and VI increased to the same extent as HSP 60 after endurance training. It appears that 16-20 weeks of endurance training leads to uniform increases in CCO subunits and parts of the transport and assembly mechanisms required for CCO enzyme assembly. The similarity among the increases in CCO subunits II and VI protein levels and the increase in CCO enzyme activity suggest that this increase in activity is due to an increase in the amount of CCO enzyme.

Effect of ovariectomy and estrogen replacement on cardiovascular disease in heart failure-prone SHHF/Mcc- fa cp rats.

The importance of endogenous and exogenous estrogen levels to the development of cardiovascular disease in women in controversial. The purpose of our study was to examine the effect of estrogen on the development of hypertension, cardiac hypertrophy, ventricular function, and gene expression for atrial natriuretic peptide (ANP) and components of the renin angiotensin system in spontaneously hypertensive heart failure rats (SHHF/Mcc- facp). Development of hypertension was prevented in 3-month-old ovariectomized rats receiving subcutaneous 17 beta -estradiol implants (EST) compared to ovariectomized (OVX) and controls (CON). EST had the least left ventricular hypertrophy, CON were intermediate, and OVX had the most (P<0.05), correlating well with systolic blood pressure. OVX had significantly lower percentage V(1)myosin isoform compared to EST and CON, indicating reversion to a more immature phenotype associated with hypertrophy. Similarly, OVX had decreased percentage left ventricular shortening fraction by echocardiography compared to EST and CON. These changes were not accompanied by alterations in plasma ANP, or in expression of mRNA for left ventricular ANP, renal renin, or hepatic angiotensinogen. Serum angiotensin converting enzyme activity was lower in EST compared to CON or OVX. When 17 beta -estradiol was given to 17-month-old rats that had naturally ceased estrous cycling, there was no effect on hypertension, progression of cardiac functional decline, or survival. In conclusion, estradiol treatment given prior to the development of hypertension in SHHF prevented left ventricular hypertrophy and hypertension. Development of congestive heart failure was not delayed if 17 beta -estradiol was begun in the post-menopausal period. Effectiveness of estrogen therapy may depend on age or whether hypertension is already established at the time treatment is begun.

Heart murmurs, valvular regurgitation and electrical disturbances in copper-deficient genetically hypertensive, hypertrophic cardiomyopathic rats.

OBJECTIVE: Rats with a genetic tendency to develop hypertensive, hypertrophic cardiomyopathy were fed copper-deficient diets and their cardiac responses were investigated. METHODS: Five male weanling rats of the Long-Evans and SHHF/Mcc-fa(cp) strains were randomly selected to receive diets containing either adequate quantities of copper (94.5 micromol Cu/kg diet) or reduced quantities of copper (<15.8 micromol Cu/kg diet) for 6 weeks, (n=5 within each group). Echocardiograms and electrocardiograms were recorded and analyzed at the end of the 6-week interval. RESULTS: Electrocardiograms from copper deficient groups showed longer Q-T intervals and increased QRS amplitudes than controls. Both the copper deficient and control SHHF groups demonstrated significant QRS complex prolongation compared to Long-Evans rats. Echocardiography analysis showed significant increases in left ventricular area, free wall dimension, and myocardial cross-sectional areas in rats fed a copper deficient diet. The frequency of systolic cardiac murmurs increased in copper deficient rats and were related to the presence of valvular regurgitation as determined from echocardiography. DISCUSSION: However, the data do not suggest that a copper-deficient diet fed to a strain of rats genetically susceptible to heart disease later in life, hastens or worsens the onset of cardiac disease. The genetic predisposition and copper-deficient states exert independent effects upon the heart.