Donate NowDr. Arthur GuytonEmployment OpportunitiesCore Facilities
  • Research Summary of Thomas Lohmeier, PhD

    Because of an interest in understanding the neurohormonal mechanisms that are causal in the progression of hypertension, and salt and water retention in heart failure, most of our experiments have been long-term longitudinal studies and have been conducted in chronically instrumented animals, particularly dogs. In contrast to the chronic influence of many hormones on renal excretory function and arterial pressure, the role of the sympathetic nervous system in long-term control of sodium excretion and arterial pressure is poorly understood.

    While it is recognized that the sympathetic nervous system is activated in hypertension and heart failure, the mechanisms that account for this activation and the importance of the sympathetic nervous system in impairing renal excretory function and producing long-term changes in arterial pressure are unclear.

    Our recent studies indicate that renal sympathetic nerve activity is chronically suppressed and promotes sodium excretion in states of excess body fluid volume and in experimental models of secondary hypertension. This suggests that the sympathetic nervous system, via the renal nerves, plays a role in long-term regulation of body fluid volume and arterial pressure. Important goals of our research are to identify the afferent mechanisms that account for sustained renal sympathoinhibition in the above states and to determine the quantitative importance of this compensatory mechanism in attenuating sodium retention and increments in arterial pressure.

    Over the last several years a number of observations in chronically instrumented animals have indicated the baroreflex is chronically activated in hypertension and has sustained effects to inhibit renal sympathetic nerve activity, promote sodium excretion, and reduce arterial pressure. In our laboratory, support for this concept has evolved from studies employing a number of techniques in chronically instrumented dogs including: 1) renal norepinephrine spillover--an indirect index of renal nerve activity, 2) 24-h measurements of sodium excretion in dogs with hemibladders and one denervated kidney before and after sinoaortic denervation, and 3) use of Fos-like immunohistochemistry to determine activation of central neurons in the baroreflex pathway.

    Most recently, our laboratory has used a novel technique to assess quantitatively the temporal blood pressure lowering effects of baroreflex activation and the mechanisms that mediate the fall in arterial pressure. Prolonged baroreflex activation is achieved by chronic bilateral electrical stimulation of the carotid sinuses. Of particular significance, we have determined that prolonged baroreflex activation has impressive long-term effects to suppress sympathetic activity and lower blood pressure; however, the magnitude of these responses is dependent upon preexisting conditions.

    We are currently using this methodology to elucidate the mechanisms whereby prolonged baroreflex activation produces sustained reductions in arterial pressure with emphasis on baroreflex-mediated suppression of renal sympathetic nerve activity and the interaction of renal sympathoinhibition with the renin-angiotensin system in mediating this response. These studies have provided a sound physiological basis for the use of carotid baroreflex stimulation in the treatment of resistant hypertension. The efficacy of electrical stimulation of the carotid sinus for the treatment of resistant hypertension is now being evaluated in clinical trials.