Strategies for investigation of CNS mechanisms of phenotypic variation in blood pressure and salt appetite in genetic hypertensive rats.
Several characteristics of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY), make these homozygous strains particularly well suited for investigating the interactions of salt appetite, blood pressure control, and their neuroendocrine substrates. Appropriate genetic and developmental investigations of sources of variation in salt appetite, blood pressure, and their putative neuroendocrine substrates in these homozygous strains can provide valuable insights into fundamental mechanisms of disease, as well as factors controlling homeostatic behavioral and physiological processes. However, inappropriate use of these strains can produce misleading, although seductively plausible, conclusions regarding mechanisms. Selective inbreeding for hypertension has concentrated in SHR the "high pressure" allele for several genes that influence blood pressure, whereas breeding for normal blood pressure has left WKY with the "normal pressure" allele for all or most of these genes. In principle, inbred hypertensive strains could provide information about specific genetic alterations that mediate the hypertensive phenotype. The benefits of work with these strains are discussed, but several false assumptions and logical pitfalls are described that might cause misleading or erroneous interpretations of results from work with such strains. These problems illustrate the importance of the research strategy in elucidating the particular information that can be provided by these inbred animal models of hypertension. Two strategic approaches for studying hypertension and other genetically determined or influenced characteristics in inbred animal models such as SHR are discussed: cosegregation analysis for identifying or rejecting genetic linkage, and brain graft techniques for identifying brain specific genetic influences on cardiovascular or behavioral phenotypes. Examples of each approach are described.
Yongue
B G
BG
Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY.
D000818:Animals; D001066:Appetite; D001794:Blood Pressure / Q000235:genetics*; D002490:Central Nervous System / Q000503:physiopathology*; D014644:Genetic Variation; D010641:Phenotype; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012965:Sodium Chloride
D012965:Sodium Chloride