The spontaneously hypertensive rat (SHR) has an enhanced tubuloglomerular feedback (TGF) and a diminished buffering by juxtaglomerular apparatus (JGA)-derived NO. We examined the hypothesis that these effects are due to decreases in nitric oxide synthase (NOS) expression or limited availability of l-arginine or tetrahydrobiopterin (BH4). SHR had significantly ( P < 0.05) greater mRNA abundance (by RT-PCR) or protein (by Western analysis) for neuronal NOS (nNOS, or type I) and endothelial cell NOS (ecNOS, or type III) in renal cortex or isolated glomeruli, respectively. There was prominent expression of ecNOS in glomerular endothelium and nNOS in macula densa. Maximal TGF responses, assessed from changes in proximal stop-flow pressure during orthograde loop of Henle (LH) perfusion, were greater in SHR [Wistar-Kyoto (WKY), 8.1 ± 0.3 ( n = 46) vs. SHR, 10.3 ± 0.3 mmHg ( n = 57); P < 0.001]. Unlike WKY, TGF responses of SHR were unresponsive to microperfusion of the nNOS inhibitor, 7-nitroindazole (7-NI, 10−4 M) [WKY, 9.5 ± 0.5 to 13.2 ± 0.7 ( n = 13, P < 0.001) vs. SHR, 11.8 ± 0.7 to 12.5 ± 0.6 mmHg ( n = 19, not significant)], or tol-arginine (10−3 M) [WKY, 7.7 ± 0.8 to 6.3 ± 0.4 ( n = 10, P < 0.05) vs. SHR, 10.4 ± 0.7 to 10.6 ± 0.7 mmHg ( n = 10, not significant)]. Neither BH4(10−4 M) nor sepiapterin (10−4 M), its stable precursor, modified TGF responses in WKY or in SHR, nor did they restore a response to microperfusion of 7-NI in SHR. In conclusion, there is a diminished role for NO from nNOS in blunting of TGF in SHR which cannot be ascribed to limited NOS expression or availability of substrate or BH4.

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An altered role of AQP2 water channels in DOCA-salt hypertension was investigated. DOCA-salt hypertension was induced in rats. Control groups were either treated with DOCA alone or subjected to a high-salt intake without DOCA. Four weeks after inducing the hypertension, AQP2 expression and shuttling were determined in the kidney. Adenylate cyclase activity was also determined to examine the upstream affecting the AQP2 system. The AVP-evoked cAMP generation in the cortex and outer medulla was augmented following the treatment with DOCA either alone or combined with high-salt intake. Accordingly, the expression and shuttling of AQP2 proteins were increased in the cortex and outer medulla. These findings suggest that DOCA enhances cAMP generation and expression/shuttling of AQP2 water channels in the kidney, which may be causally related with the development of hypertension.

We describe a 64-year-old male patient with panhypopituitarism who experienced polymorphic ventricular tachycardia (VT) associated with long QT intervals. The panhypopituitarism developed as a sequelae of radiation therapy administered 20 years prior to his current presentation and was recently aggravated by urinary tract infection with sepsis. In this case, polymorphic VT was resistant to conventional therapy (including magnesium infusion), and QT prolongation and T wave inversion were normalized after the administration of steroid and thyroid hormones. Thyroid hormone is generally known to be associated with torsades de pointes (TdP), but steroid or other hormones may also provoke TdP. Hormonal disorders should be considered as a cause of polymorphic VT with long QT intervals. Some arrhythmias can be life-threatening, and they can be prevented with supplementation of the insufficient hormone.