Teaching: Pharmacology, Physiology
Dr. Heesch’s research is focused on central nervous system regulation of blood pressure and efferent sympathetic nerve activity in both physiological and pathophysiological states, such as hypertension. A major emphasis in the laboratory is examining the role of neuromodulators such as nitric oxide and ovarian hormones (and metabolites) on plasticity of CNS regulation of the cardiovascular system.
During pregnancy ovarian hormones are elevated and previous work in the Heesch laboratory has demonstrated that CNS effects of the major metabolite of progesterone contribute to the attenuated sympathoexcitatory responses in pregnant animals. Understanding the mechanisms for attenuated sympathoexcitation in normal pregnancy, will contribute to determining mechanisms for elevations of arterial blood pressure in hypertensive disorders of pregnancy, where sympathoexcitatory responses are exaggerated. The possibility that a metabolite of progesterone, 3 alpha-OH-dihydroprogesterone, may play a major role in suppression of sympathoexcitatory responses is especially intriguing. 3 alpha-OH-dihydroprogesterone is produced in the brain of both males and females and is the most potent endogenous positive modulator of central nervous system GABAA receptors. Since sympathoinhibition is produced centrally through activation of GABA receptors and since this compound does not produce endocrine effects like estrogen and progesterone, it could have important implications for the control of hypertensive disorders in males as well as females.
Experimental questions are addressed in whole animal physiology experiments, as well as cellular and molecular experiments. Commonly used techniques include: Measurement of hemodynamic parameters (ex./ heart rate & arterial blood pressure); recording of afferent and efferent nerve activity; and CNS microinjection of putative transmitters and modulators. Expression of receptors, transmitters, and enzymes of interest are evaluated in micropunches from brain tissue or in individual cells collected by laser capture microscopy.
Laiprasert, J.L., R.C. Rogers, C.M. Heesch. Neurosteroid modulation of arterial baroreflex sensitive neurons in the rostral ventrolateral medulla of the rat. Amer. J. Physiol., 274: R903-R911, 1998. [Abstract]
Foley, C.M., J.J. Stanton, E.M. Price, J.T. Cunningham, E.M. Hasser, and C.M. Heesch. GABA(A) alpha 1 and alpha 2 receptor subunit expression in rostral ventrolateral medulla in nonpregnant and pregnant rats. Brain Research 975: 196-206, 2003. [Abstract]
Foley, C.M., P.J. Mueller, E.M. Hasser and C.M. Heesch. Hindlimb Unloading and Female Gender Attenuate Baroreflex Mediated Sympathoexcitation. Amer. J. Physiol. (Regulatory, Integrative, & Comparative Physiol.), 289: R1440-7, 2005. [Abstract]
Mueller, P.J., C.M. Foley, C.M. Heesch, J.T. Cunningham, Z. Hong, K.P. Patel, E.M. Hasser. Increased nitric oxide synthase activity and expression in the hypothalamus of hindlimb unloaded rats. Brain Research, 1115: 65-74, 2006. [Abstract]
Heesch, C.M., J.D. Laiprasert, L. Kvochina. RVLM glycine receptors mediate GABAA and GABAB independent sympathoinhibition from CVLM in rats. Brain Research, 1125: 46-59, 2006. [Abstract]
Kvochina, L, EM Hasser and CM Heesch. Pregnancy increases baroreflex independent GABAergic inhibition of the RVLM in rats. Amer. J. Physiol. (Regulatory, Integrative & Comparative Physiol.) 293: R2295 – 305, 2007.[Abstract]