Abstract

The TGR(mREN2)27, transgenic homozygous (TH) rat strain is severely hypertensive, and unless treated, only 20% of males and 50% of the females survive past 20 weeks of age. Losartan-treated TH male rats are mated with normotensive female Hannover Sprague-Dawley (HnSD) rats to produce less hypertensive hemizygous (HEMI-) TGR(mREN2)27 rats with systolic blood pressure (SBP) ~180-200 mm Hg for females and males at ~20 weeks of age, allowing experimental study without antihypertensive treatment. Helicobacter species infection, which in rodents causes gastro-intestinal and hepatic disturbances and inflammation, compromised immunity and decreased breeding success, was detected in our TH and HnSD breeding colonies. Eradication improves animal health and breeding outcomes. However, the effects of Helicobacter diet treatment on phenotypic characteristics of the HEMI-TGR(mREN2)27 are unknown. TH and HnSD rats from the original WFSM colony were isolated and treated in a clean room for 8-12 weeks with Mouse Diet, Helicobacter 4 Drug Combo (Bio-Serv., Frenchtown, N.J.; pelleted diet containing 3.0 mg Amoxicillin, 0.5 mg Clarithromycin, 1.0 mg Metronidazole, 0.02 mg Omeprazole per 5 grams). Eight male and six female offspring from TH X HnSD rats and five male and six female HnSD X HnSD rats from diet-treated parents with confirmed infection eradication had tail-cuff SBP measured at 20 weeks of age for comparison with rats from the original non-treated colony. The SBPs were similar between control and treated female HEMI-TGR(mREN2)27 (191 ± 8 vs 184 ± 7 mm Hg) and between control and treated male HEMI-TGR(mREN2)27 groups (194 ± 4 vs 182 ± 3 mm Hg). Also, SBP was not different between female or male, control vs treated, HnSD rats (Female: 130 ± 6 vs 121 ± 5 mm Hg; Male:130 ± 1 vs 136 ± 5 mm Hg). Consistent with previous studies, male HEMI-TGR(mREN2)27 rats weighed significantly more than male HnSD rats (516 ± 10 vs 454 ± 16 g, p<0.01), while female mRen and female HnSD were similar (280 ± 8 vs 255 ± 4 g). Therefore, Helicobacter treatment and eradication in homozygous parental TGR and HnSD lines did not alter the hypertensive phenotype in HEMI-TGR(mREN2)27 rats, nor change the normotensive phenotype of HnSD rats.

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