Physiological Significance of Macula Densa Neuronal Nitric Oxide Synthase-1 in Renin Release and Renin-dependent Blood Pressure Maintenance

Abstract

The role of macula densa nitric oxide synthase 1 (NOS1) in regulation of renin release is controversial. This study was conducted to further elucidate the role of macula densa NOS1 in renin release and blood pressure regulation in response to salt challenges and hemorrhagic shock.Tissue specific macula densa-NOS1 knockout (KO) and wild type (WT) mice were given low (0.1% NaCl) and high (1.4% NaCl) sodium diets or induced hemorrhagic shock by retro-orbital bleeding of 0.4 ml blood. Mean arterial pressure (MAP) was measured by radio-telemetry system. Plasma renin concentration (PRC) was determined by radioimmunoassay.PRCs were 496 ± 74 and 552 ± 68 ng/ml/hr in WT and KO mice fed a normal sodium diet, respectively. Low salt intake stimulated the renin release by about 220% in WT mice (PRC = 1364 ± 217 ng/ml/hr) compared to the level of normal salt diet, however, the stimulation was significantly blunted in KO mice (PRC = 688 ± 104 ng/ml/hr). High salt intake suppressed the PRC to the level of about 61% of PRC under normal salt diet. Deletion of macula densa-NOS1 further inhibited renin release to 43% of the levels of normal salt diet.Hemorrhagic shock induced about a 3-fold increase in PRC in WT mice, while only about 54% increase in the KO mice. The MAP values were significantly higher in WT mice than in KO mice during the first 6 hours following hemorrhagic shock. Thus, WT mice showed much quicker recovery in MAP than KO mice.Our study demonstrated that macula densa NOS1 plays an important role in mediating renin release. This mechanism is essential in maintaining blood pressure under hypovolemic situations such as hemorrhagic shock. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.