Key result
Injection of losartan and aminoguanidine into the RVLM reduced mean arterial pressure by 11% and 31%, and renal sympathetic nerve activity by 18% and 34%, respectively, in 2K-1C hypertensive rats.
Upregulation of AT1R and iNOS in the RVLM is essential for maintaining high blood pressure and sympathetic hyperactivity in the 2K-1C rat model of hypertension.
Central AT1R/iNOS inhibition merits exploration as antihypertensive strategy; leaves open human translation from this animal model.
BACKGROUND: We hypothesized that upregulation of angiotensin type 1 receptor (AT(1)R) and inducible nitric oxide (NO) synthase (iNOS) within the rostral ventrolateral medulla (RVLM) could contribute to two-kidney, one-clip (2K-1C) hypertension. METHODS: The experiments were performed in male Wistar rats, 6 weeks after the renal surgery. The animals were divided into control (SHAM, n = 18) and hypertensive groups (2K-1C, n = 18). Bilateral tissue punches were taken from sections containing the RVLM to perform iNOS gene expression analyses by the real-time PCR technique, and AT(1)R and iNOS protein expression analyses by western blotting. In addition, we injected losartan (1 nmol), an AT(1)R antagonist, and aminoguanidine (250 pmol), an iNOS inhibitor, bilaterally into the RVLM to analyze the mean arterial pressure (MAP) and renal sympathetic nerve activity (rSNA). RESULTS: iNOS mRNA expression levels were greater (P < 0.05) in the 2K-1C group compared to the SHAM group. Furthermore, the AT(1)R and iNOS protein expression were significantly increased in the RVLM of 2K-1C rats compared to SHAM rats. Injection of losartan into the RVLM reduced the MAP (11%) and rSNA (18%) only in the 2K-1C rats, whereas injection of aminoguanidine in the same region decreased the MAP (31%) and rSNA (34%) in hypertensive rats. CONCLUSIONS: The present study suggests that upregulation of AT(1)R and iNOS in the RVLM is important in the maintenance of high blood pressure and renal sympathetic activation in 2K-1C hypertension.
No takes yet. Share an insight, caveat, or question.
Oliveira‐Sales et al. (2010) studied 2K-1C hypertension (n=36). Losartan and aminoguanidine injection into the RVLM vs. SHAM control group was evaluated on Mean arterial pressure (MAP) and renal sympathetic nerve activity (rSNA). Injection of losartan and aminoguanidine into the RVLM reduced mean arterial pressure by 11% and 31%, and renal sympathetic nerve activity by 18% and 34%, respectively, in 2K-1C hypertensive rats.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: