Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently reported in normal isolated-perfused rat lungs that low basal tone appears to be regulated by nitric oxide (NO)-dependent and -independent mechanisms of soluble guanylate cyclase activation. In this study, we examined the role of NO in the regulation of pulmonary artery (PA) tone from rats with renin-dependent hypertension. Rats were made hypertensive by ligating the abdominal aorta above the left and below the right renal artery (aortic coarctation, AC). Mean arterial pressure significantly increased from 119 +/- 8.4 mmHg in control animals to 156 +/- 15 mmHg 7-14 days after AC surgery. PA pressures, however, remained unchanged (8.5 +/- 3.4 mmHg in control animals vs. 11 +/- 3.3 mmHg in AC animals). Hypoxic contractions in U-46619 precontracted isolated small PA (160-260 microns diameter) were significantly increased from 51 +/- 13 mg in the control group to 142 +/- 38 mg (P < or = 0.05) in AC animals. Nitro-L-arginine (NLA; 100 microM) contractions were also enhanced in the AC animal. The enhanced NLA response may correlate with an increase in endothelial cell NO synthase (NOS) as detected by Western blotting (132 +/- 28% of control; P < 0.05). These data suggest that, in this renin-dependent model of systemic hypertension, there is increased endothelial cell NOS activity that maintains low PA tone, preventing the lung from developing increased pressures.
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PMID:Peripheral hypertension and alterations in pulmonary vascular regulation. 925 47

In the present study we searched for quantitative trait loci (QTLs) that affect neuroendocrine stress responses in a 20-min restraint stress paradigm using Brown-Norway (BN) and Wistar-Kyoto-Hyperactive (WKHA) rats. These strains differed in their hypothalamic-pituitary-adrenal axis (plasma ACTH and corticosterone levels, thymus, and adrenal weights) and in their renin-angiotensin-aldosterone system reactivity (plasma renin activity, aldosterone concentration). We performed a whole-genome scan on a F2 progeny derived from a WKHA x BN intercross, which led to the identification of several QTLs linked to plasma renin activity (Sr6, Sr8, Sr11, and Sr12 on chromosomes RNO2, 3, 19, and 8, respectively), plasma aldosterone concentration (Sr7 and Sr9 on RNO2 and 5, respectively), and thymus weight (Sr10, Sr13, and Srl4 on RNO5, 10, and 16, respectively). The type 1b angiotensin II receptor gene (Agtrlb) maps within the confidence intervals of QTLs on RNO2 linked to plasma renin activity (Sr6, highly significant; LOD = 5.0) and to plasma aldosterone level (Sr7, suggestive; LOD = 2.0). In vitro studies of angiotensin II-induced release of aldosterone by adrenal glomerulosa cells revealed a lower receptor potency (log EC50 = -8.16 +/- 0.11 M) and efficiency (Emax = 453.3 +/- 25.9 pg/3 x 10(4) cells/24 h) in BN than in WKHA (log EC50 = -10.66 +/- 0.18 M; Emax = 573.1 +/- 15.3 pg/3 x 10(4) cells/24 h). Moreover, differences in Agtr1b mRNA abundance and sequence reinforce the putative role of the Agtr1b gene in the differential plasma renin stress reactivity between the two rat strains.
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PMID:QTL mapping for traits associated with stress neuroendocrine reactivity in rats. 1615 95

Voltage-dependent Ca(2+) channel function (Ca(v)1.2, L-type Ca(2+) channel) is required for cardiac excitation-contraction (E-C) coupling. Ca(v)1.2 plays a key role in modulating cardiac function in response to classic signaling pathways, such as the renin-angiotensin system and sympathetic nervous system. Regulation of cardiac contraction by neurotransmitters and hormones is often correlated with Ca(v)1.2 current through the actions of cAMP and cGMP. Cardiac cGMP, which activates protein kinase G (PKG), is regulated by nitric oxide (NO), and natriuretic peptides. Although PKG has been reported to activate or inhibit Ca(v)1.2 function, it is still unclear whether Ca(v)1.2 subunits are PKG substrates. We have identified phosphorylation sites within the alpha(1c) and beta(2a) subunits that are phosphorylated by PKGIalpha in vitro. We demonstrate that a subset of these phosphorylation sites is modulated, in a cGMP-PKG-specific manner, in intact HEK cells heterologously expressing alpha(1c) and beta(2a) subunits. Using phospho-epitope-specific antibodies, we show that the phosphorylation of these residues is enhanced by PKG in intact cardiac myocytes. Activation of PKG in HEK cells transfected with alpha(1c) and beta(2a) subunits caused an inhibition of Ca(v)1.2 whole-cell current. PKG-mediated inhibition of Ca(v)1.2 current was significantly reduced by coexpression of an alanine-substituted Ca(v)1.2 beta(2a) subunit (Ser(496)). Our results identify a molecular mechanism by which cGMP-PKG regulates Ca(v)1.2 phosphorylation and function.
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PMID:Protein kinase G phosphorylates Cav1.2 alpha1c and beta2 subunits. 1762 95