The project is directed at interactions between sympathetic nervous systems (SNS) activity and biological response of adrenoceptors at the junction with the vasculature. The hypothesis is that blood pressure deviates from normal when there is an imbalance between SNS impulse frequency and response of postsynaptic excitatory receptors and/or presynaptic inhibitory receptors on the nerve terminal. An ontogenetic approach focuses on developmental periods when blood pressure control mechanisms are becoming functional in a highly altrical species, the rat. Models of genetically determined and environmentally induced defects in blood pressure are studied. The spontaneously hypertensive rat (SHR) is hypertensive from birth. The Sprague-Dawley rat (SD) nursed by stressed dams (SSD) is a new model for environmentally induced defect which is hypertensive at weaning and hypotensive as adult. Using anesthetized preparations, ontogeny of sympathetic outflow, modulating reflexes and biological response of Alpha-1, Alpha-2 cardiovascular adrenoceptors is studied in SHR-WKY (control) and SSD-SD (control). Preganglionic SNS action potentials are recorded. Parameters evaluated are: resting and maximum frequency; baroreflex gain (-Hz/mm Hg pressure ramp) and hypoxic chemoreflex gain (Hz/-FIO2). Biological response of vascular receptors is assessed by measuring potencies of highly selective alpha-1, -2 adrenoceptor antagonists against pressor responses to electrical stimulation of SNS and i.v.NE in pithed preparations. Cardioaccelerator responses to electrical stimulation (beta) are tested against doses of a selective alpha-2 agonist and antagonist to assess biological response of presynaptic inhibitory alpha-2 receptors. Experiments are performed at times between birth and 80 days postnatally when significant developments in blood pressure control are known to occur: onset of ganglionic neurotransmission, onset of baroreflex, period of SNS hyperactivity, period of accelerated BP maturation in SHR-WKY; periods of hyper- and hypotension in SSD. Measurements will reveal how the biological responses of adrenoceptors adjusts to maturation of impulse outflow in normotension and in two forms of experimental hypertension. Information gained should advance understanding of human essential hypertension.
