CARDIOVASCULAR REGULATION IN HEALTH AND DISEASE

Synopsis

The role of cardiovascular receptors in the neural regulation of circulatory system is now well established. Atrial type B receptors located in the two atria and veno-atrial junctions, which are stimulated by atrial filling are believed to play an important role in the regulation of body fluid volume and heart rate. Heart rate is influenced also by other sensory receptors e.g. arterial baroreceptors, ventricular receptors, pulmonary stretch receptors and chemoreceptors. Of all these visceral receptors, arterial baroreceptors located mainly in the aortic arch and the carotid sinus region are stimulated by intravascular pressure; play a major role in the regulation of blood pressure by changes in heart rate and vascular tone. The vascular tone is also affected by the circulatory levels of various neurotransmitters and hormones. Vasodilatory response to adenosine and acetylcholine is partly mediated through endothelium-derived relaxing factors (EDRF), hyperpolarizing factors (EDHF) and contracting factors (EDCF). The endothelium-dependent mechanisms are altered during hypertension and diabetes. The autonomic control of blood pressure is primarily through arterial baroreceptors. The sensitivity of the baroreceptor heart rate reflex is significantly attenuated on occlusion of left anterior descending coronary artery (LAD) of anaesthetised dogs taken as an experimental model of coronary insufficiency in patients of coronary heart disease. The fall in the sensitivity of baroreflex on LAD occlusion is mediated primarily by sympathetic limb of the autonomic nervous system. Acute fall in hemoglobin level by hemodilution in dogs produced an increase in cardiac output by increasing the heart rate through inhibition of parasympathetic tone. After parasympathetic blockade the increase in cardiac output on fall in hemoglobin was due to a rise in the stroke volume. Acute fall in hemoglobin level attenuated the baroreflex response. Sustained changes in blood pressure cause resetting of baroreflex i.e. increase in arterial pressure involves reduced activity of baroreceptors at equivalent pressure and vascular stretch. Like in acute hypoxia the altered responsiveness of baroreceptor heart rate reflex during oxygen deficiency due to acute occlusion of LAD or acute normovolemic hemodilution may involve both peripheral and central components and possibility of modulation by circulating hormones also exists.

Neurohumoral disturbances characterize chronic heart failure (CHF) and are reflected as impairment of baroreflex sensitivity (BRS) and sympathetic function. However the mechanisms that trigger the neurohumoral abnormalities in CHF are not clear. We hypothesized that the BRS is blunted early in CHF and that the humoral effects occur later and contribute to progressive loss of cardiovascular control in CHF. We assessed the BRS (bpm/mmHg) and recorded renal sympathetic nerve activity (RSNA) in four groups of conscious rabbits; control, one week CHF, two week CHF and three week CHF groups. CHF was induced by ventricular pacing at 360 bpm and was assessed by echocardiography. Arterial blood pressure and heart rate were recorded by an implanted telemetric device and RSNA through an implanted electrode. A significant fall in the ejection fraction (EF), fractional shortening (FS) and an increase in left ventricular end systolic diameter (LVESD) and left ventricular end diastolic diameter (LVEDD) was observed in all CHF groups. The BRS was significantly reduced in all the CHF groups with no significant change in the basal RSNA (% of maximum) and plasma angiotensin II level (Ang II, pg/ml) after 1 week of pacing, a small but insignificant rise in RSNA and Ang II was seen at 2 weeks and a significant rise in RSNA and Ang II was observed at 3 weeks. AT l receptor protein (Western Blot) and mRNA (RT -PCR) expression in the rostral ventrolateral medulla (RVLM) exhibited a progressive increase with the duration of CHF, reaching significance after 3 weeks. These data are the first to examine early changes in central ATI receptors in CHF and suggest that the fall in BRS and hemodynamic changes occur early in the development of CHF followed by sympathoexcitation and over-expression of ATI receptors with the progression of CHF causing further impairment of cardiovascular control.