Tenofovir during pregnancy in rats: a novel pathway for programmed hypertension in the offspring

• Published in: Journal of antimicrobial chemotherapy 2015-04, Vol.70 (4), p.1094-1105
• Main Authors: Gois, Pedro Henrique França, Canale, Daniele, Luchi, Weverton Machado, Volpini, Rildo Aparecido, Veras, Mariana Matera, Costa, Natália de Souza Xavier, Shimizu, Maria Heloisa Massola, Seguro, Antonio Carlos
• Format: Article
• Language: English
• Subjects: Adenine - administration & dosage; Adenine - adverse effects; Adenine - analogs & derivatives; Animals; Antiretroviral drugs; Antiviral Agents - administration & dosage; Antiviral Agents - adverse effects; Biological Transport, Active - drug effects; Blood pressure; Female; Hypertension; Hypertension - chemically induced; Models, Animal; Organophosphonates - administration & dosage; Organophosphonates - adverse effects; Pregnancy; Rats, Wistar; Renin-Angiotensin System - drug effects; Rodents; Sodium; Sodium - metabolism; Tenofovir
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dku483

To evaluate the occurrence of systemic and renal abnormalities in the offspring of Wistar rats exposed to tenofovir disoproxil fumarate (DF) during pregnancy. Female Wistar rats received a standard diet, with or without addition of tenofovir DF (100 mg/kg diet), 1 week before mating and during pregnancy. Offspring from the tenofovir DF group were placed with an untreated foster mother during breastfeeding and compared with offspring from rats maintained on a standard diet during mating and pregnancy (control). Control and tenofovir DF were followed up at 3 and 6 months of age. Monthly body weight and systolic blood pressure (SBP), glomerular counts, renal function, biochemical parameters, angiotensin II, renal renin angiotensin aldosterone system (RAAS) and renal sodium transporters were analysed. Tenofovir DF offspring showed lower birth weight compared with the control group. After the third month, growth among the tenofovir DF group experienced a rapid catch-up. SBP increased progressively after the second month of age in the tenofovir DF group. Nephron number did not differ between the groups; however, the tenofovir DF group showed glomerular structural changes. Plasma aldosterone was higher in the tenofovir DF group, associated with a significant increase in renal expression of RAAS. The tenofovir DF rats showed up-regulation of renal sodium transporters and consequently lower urinary sodium excretion. This is the first demonstration using an experimental model that maternal exposure to tenofovir DF during gestation results in overactivation of RAAS, up-regulation of renal sodium transporters and hypertension in the offspring.