Key result
Aged male Ren-2 transgenic rats exhibited significantly elevated systolic blood pressure (208±7 mm Hg) compared to normotensive controls (150±2 mm Hg), whereas female transgenic rats were normotensive.
Why the study?
Sex-related differences are observed in human and experimental hypertension, prompting comparison of blood pressure in aged male and female heterozygous Ren-2 transgenic rats versus normotensive controls.
Does the Ren-2 transgene cause sex-dependent differences in blood pressure, oxidative stress, and lipid metabolism in aged rats?
Does the Ren-2 transgene cause sex-dependent differences in blood pressure, oxidative stress, and lipid metabolism in aged rats?
Absolute Event Rate: 208% vs 150%
p-value: p=≤0.05
Aged Ren-2 transgenic rats exhibit marked sexual dimorphism in blood pressure, with males remaining hypertensive and females becoming normotensive, independent of oxidative stress or abnormal cholesterol metabolism.
Sexual dimorphism in Ren-2 hypertension persists independent of oxidative stress or lipids; hypothesis-generating for mechanisms and human translation.
Sex-related differences were observed not only in human but also in experimental hypertension. The aim of our study was to compare blood pressure (BP) of aged male and female heterozygous transgenic rats (TGR) harboring Ren-2 mouse gene, with their normotensive Hannover Sprague-Dawley (HanSD) controls. At the age of 9 months, systolic (SBP) and diastolic blood pressure (DBP) were measured by a direct puncture of carotid artery in rats awaking from isoflurane anesthesia. Thiobarbituric acid-reactive species (TBARS) formation was monitored as indicator of lipid peroxidation damage in heart, kidney and liver, whereas intracellular content of reduced glutathione was determined in the same organs as the main intracellular antioxidant. Furthermore, plasma triglycerides and total cholesterol as well as high-density lipoprotein (HDL) and low-density lipoprotein (LDL) fractions of cholesterol were measured. As compared to HanSD rats, we found significantly elevated BP only in male TGR (MAP: 123±1 vs. 171±5, SBP: 150±2 vs. 208±7, and DBP: 99±3 vs. 140±4 mm Hg), but not between TGR and HanSD females, which were both normotensive. We also did not find any significant differences in TBARS and reduced glutathione in the three above mentioned organs as well as in plasma cholesterol or its HDL and LDL fractions between transgene-negative HanSD and TGR animals of either sex. However, we found significant sex differences in TBARS, glutathione and plasma lipids in both rat strains. Our results confirmed that aged TGR exhibit a marked sexual BP dimorphism, which does not seem to be dependent on oxidative stress or abnormal cholesterol metabolism.
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Rauchová et al. (2020) studied Hypertension (n=27). Ren-2 transgenic rat model (male) vs. Hannover Sprague-Dawley controls and female TGR was evaluated on Systolic blood pressure (SBP) (p=≤0.05). Aged male Ren-2 transgenic rats exhibited significantly elevated systolic blood pressure (208±7 mm Hg) compared to normotensive controls (150±2 mm Hg), whereas female transgenic rats were normotensive.
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