Involvement of Endothelial Nitric Oxide Synthase Activation in Midkine-Mediated Central Hypotensive Effects.

In this study, we investigated whether the renin-angiotensin system and/ or N-methyl-D-aspartate (NMDA) receptor-calmodulin-eNOS signaling pathways were both involved in midkine-mediated blood pressure (BP) regulation in the NTS of Wistar-Kyoto rats. Intra-NTS microinjection and immunoblot analysis were used to evaluate the signal pathway. WKY rats were anesthetized with urethane. Unilateral microinjection of midkine (600 fmol) into the NTS produced a dose-dependent decrease in BP and heart rate (HR). The depressor effects were observed before and after microinjection of the angiotensin-converting-enzyme (ACE) inhibitor lisinopril (2.4 fmol), or the angiotensin receptor blockers (ARB) inhibitor valsartan (7.5 pmol). However, lisinopril and valsartan did not diminish the midkine-mediated cardiovascular effects in the NTS. Microinjection of the NMDA receptor antagonist MK801 (1 nmol) or the NOS inhibitor L-NAME, (33 nmol), into the NTS attenuated the midkine-induced hypotensive effects. Pretreatment with an eNOS inhibitor L-NIO (6 nmol) attenuated the midkine-induced hypotensive effects. In this study, the data showed that midkine might play a role in central cardiovascular regulation in the NTS. These results suggest that midkine decreased BP and HR in the NTS probably acting via the NMDA receptor-calmodulineNOS signaling pathway. PMID: 29241309 [PubMed - as supplied by publisher]
Source: The Chinese Journal of Physiology - Category: Physiology Tags: Chin J Physiol Source Type: research