Heart mass and blood pressure have separate genetic determinants in the New Zealand genetically hypertensive (GH) rat.
OBJECTIVE
To determine associations between cardiovascular parameters and genotype in 205 F2 rats of both sexes and lineages from reciprocal crosses made between rats of the New Zealand genetically hypertensive (GH) and Brown Norway (BN) rat strains.


METHODS
Systolic tail blood pressure, mean arterial blood pressure, pulse rate, heart mass, body mass and relative heart mass were determined for each rat in the age range 17-19 weeks, and DNA polymorphisms were examined for the guanylyl cyclase A (GCA), angiotensin converting enzyme (ACE) and renin (REN) genes.


RESULTS
The phenotypic data indicated the presence of genes on the X and Y chromosomes that affected blood pressure. The GH GCA allele, in males only, and the GH ACE allele, in females only, both cosegregated with increased blood pressure. The ACE effect was confined to rats of one lineage only, namely those with GH grandfathers. A cosegregation of the GH REN allele with decreased blood pressure was also detected in females with BN grandfathers. In contrast, the GH REN allele cosegregated with a smaller heart in males only, whereas the GH ACE allele cosegregated with a larger heart both in males and in females. In males this was the consequence of a decrease in body mass with no change in absolute heart mass, whereas in females there were changes in both of these parameters.


CONCLUSIONS
The results show that cardiac hypertrophy and blood pressure have independent genetic determinants in the GH rat, and indicate the importance of sex in determining the phenotypic expression of genes underlying cardiovascular pathology.
Harris
E L
EL
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Phelan
E L
EL
Thompson
C M
CM
Millar
J A
JA
Grigor
M R
MR
D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology; D006332:Cardiomegaly / Q000235:genetics* / Q000503:physiopathology; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D006162:Guanylate Cyclase / Q000235:genetics; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008969:Molecular Sequence Data; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D051381:Rats; D011914:Rats, Inbred BN; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics; D012083:Renin / Q000235:genetics; D012730:Sex Chromosomes / Q000235:genetics
D004247:DNA; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A