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University of Wyoming

Faculty, Staff and Graduate Assistants

Bruce W. Culver
Personal biography

Bruce W. Culver
Professor
Neurotoxicology; Developmental Neurobiology

B.S. University of Wyoming
Ph.D. University of Kansas
culver@uwyo.edu • (307) 766-6481

Research:
Developmental effects of dietary NaCl on hypertension, nociception, and salt preference in spontaneously hypertensive rats (SHRs).

We have been studying brain mechanisms involved in cardiovascular regulation and nociception. The clear involvement of some of the brain regions that integrate nociceptive information in cardiovascular modulation may indicate a role in nociceptive-cardiovascular modulation. Also altered nociceptive processing has been reported in animals, including humans, with hypertension. We have demonstrated a diminished responsiveness of spontaneously hypertensive rats (SHRs) to noxious stimuli (hot plate, tail flick, and formalin tests) compared to normotensive Wistar Kyoto (WKY) control rats. To further investigate mechanisms involved in nociceptive-cardiovascular regulation we are conducting the following studies:

• Evaluation of c-fos expression in brains of SHRs and WKY rats following formalin-induced nociception. These studies will examine a number of brain areas, particularly those areas such as the nucleus tractus solitarius, locus coeruleus, caudal ventrolateral medullary and other brainstem nuclei, periaqueductal gray and hypothalamic nuclei involved in nociceptive signaling and cardiovascular modulation. The hypothesis that SHRs which show a diminished formalin response will also exhibit a diminished c-fos expression in those areas involved in nociceptive signaling will be tested.

• Examination of the effects of differences in perinatal sodium chloride exposure. Dietary salt intake affects development of the hypertensive phenotype of the SHRs when administered during critical periods of development. Collaborative studies with Dr. Bill Flynn measuring baroreceptor responsiveness in SHRs and WKY rats should provide information useful in understanding mechanisms of altered development of blood pressure produced by exposure to low or high dietary salt. It is also of interest to determine if this environmental manipulation will also affect the nociceptive phenotype of SHRs, as measured by hot plate and tail flick tests. Adult SHRs have also been shown to over-consume sodium chloride so we are also comparing this behavior in SHRs and WKY rats that had received low, normal, or high dietary salt during the perinatal period. Finally, SHRs show hyperactivity and have been used as a model of attention deficit disorder (ADD). The effects of different perinatal salt exposures on subsequent locomotor activities will be measured in SHRs and control WKY rats. Together, these studies will provide information useful in evaluating the impact of differences in salt concentration, as an environmental factor, on subsequent development of hypertension, nociceptive responsiveness, and other behaviors in a model of genetic hypertension.

• Morphological studies of brains of SHRs. Morphological differences have been reported in the brains of SHRs compared to normotensive WKY rats. One of the most obvious differences in the brains of these animals is a significant dilation of cerebral ventricles of SHRs. Other studies have reported that neither increased intraventricular pressure nor high blood pressure is the sole cause of ventricular dilation. Thus, an unknown mechanism could be implicated in the pathophysiology of the hydrocephalus seen in these genetically hypertensive rats. We will conduct a computerized morphometric analysis of the development of the ventricles, choroid plexus, and periventricular brain areas in SHRs and control rats. The effects of the different perinatal salt exposures described above on morphological development of the brain will be compared. Since dietary salt can alter the phenotypic expression of hypertension, it is of interest to see if brain maturation is affected by this environmental manipulation. These studies also provide a logical starting point to address structural-functional correlates of brain alterations in the SHR model in subsequent studies.

Publications:

REFEREED JOURNAL ARTICLES

2005

McBride, S.M., Culver, B., & Flynn, F.W. (2005). Prenatal and early postnatal salt experience affects motor responses to amphetamine in adult male WKY and SHR rats. Abstracts Society for Neuroscience, 30.

2004

Ren J, Zhang X, Scott GI, Esberg LB, Ren BH, Culver B, Chen AF. Adenovirus gene transfer of recombinant eNOS enhances contractile function in ventricular myocyte. J. Cardiovasc. Pharm. 43: 171-177, 2004.

2003

Flynn, F.W., Culver, B, and Newton, S.V. (2003). Salt intake by spontaneously hypertensive rats. Physiology & Behavior, 78: 689-696.

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