Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four inhibitors of nitric oxide synthase (NOS), administered as acute pretreatments, attenuated several signs of naloxone-precipitated opioid withdrawal in morphine-dependent rats. Profiles of these drugs for inhibiting the expression of withdrawal were similar to that of clonidine, a drug used clinically to treat opioid withdrawal. The nonselective NOS inhibitors, NG-nitro-L-arginine and NG-nitro-L-arginine methyl ester, and N(5)-(1-iminoethyl)-L-ornithine, a selective inhibitor of endothelial NOS, Increased blood pressure in awake, morphine-naive and morphine-dependent rats not undergoing withdrawal. 7-Nitroindazole, a selective inhibitor of neuronal NOS, did not elevate blood pressure. Insofar as hypertension is a component of opioid withdrawal in humans, the ability of 7-nitroindazole to attenuate morphine withdrawal in rats without eliciting a vasopressor response suggests that 7-nitroindazole may have human therapeutic potential. Research directions for the continued development of 7-nitroindazole as a therapeutic modality are discussed with respect to issues of physical dependence, tolerance, and safety.
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PMID:Nitric oxide synthase inhibitors. Preclinical studies of potential use for treatment of opioid withdrawal. 874 56

NO produced by neuronal NO synthase (nNOS) in the macula densa blunts tubuloglomerular feedback (TGF). nNOS activity is strongly pH-dependent. Increasing luminal NaCl concentration increases nNOS activity, NO production, and apical Na+/H+ exchange. Na+/H+ exchange alkalinizes the macula densa. We hypothesized that inhibiting apical Na+/H+ exchange in macula densa cells would augment TGF by blunting nNOS activation caused by increasing luminal NaCl concentration. Rabbit afferent arterioles and attached macula densas were microperfused in vitro. TGF response was defined as the change in afferent arteriole diameter caused by increasing the NaCl concentration in the macula densa perfusate. 7-Nitroindazole (7-NI; 10 micromol/L) alone in the macula densa lumen increased the TGF response from 2.4+/-0.1 to 3.8+/-0.2 microm (P<0.01). When dimethyl amiloride (100 micromol/L), a Na+/H+ exchange inhibitor, was added to the macula densa lumen, it increased the TGF response from 2.5+/-0.3 to 3.7+/-0.5 microm (P<0.01). In the presence of dimethyl amiloride, 7-NI had no effect on the TGF response (from 2.6+/-0.2 to 2.7+/-0.2 microm). Our data indicate that inhibiting apical Na+/H+ exchange in the macula densa mimics the effect of inhibiting NO production by nNOS in the macula densa on TGF. Thus, it is possible that increased apical Na+/H+ exchange caused by increasing the sodium concentration in the lumen of the macula densa activates macula densa nNOS. The link between nNOS and Na+/H+ exchange may be intracellular pH.
Hypertension 2003 Mar
PMID:Inhibition of apical Na+/H+ exchangers on the macula densa cells augments tubuloglomerular feedback. 1262 80

Nitric oxide (NO*) plays an important role in various physiological processes. The aim of the present study was to investigate if brain mitochondrial nitric oxide synthase (mtNOS) is active and functional during hypertension. L-citrulline production, an indicator of nitric oxide synthesis, was concentration-dependent on L-arginine in all strains and all ages tested, and was inhibited by 7-Nitroindazole (7-NI). Brain mitochondria of 1 month-old (prehypertensive) spontaneously hypertensive rats (SHR) exhibited a significantly (p < 0.05) low basal L-citrulline content as compared to age-matched Wistar (W) and Wistar-Kyoto (WKY) rats. L-citrulline synthesis in SHR rats showed a significant (p < 0.01) low response to L-arginine in 3 and 7 months-old rats. Respiratory rates in states 3 and 4 increased with low L-arginine concentration in all strains and all ages. The results suggest that in rat brain mitochondria, L-citrulline synthesis is constant once age-related hypertension is installed and NO* does not regulate oxidative phosphorylation.
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PMID:Functional characterization of brain mitochondrial nitric oxide synthase during hypertension and aging. 1599 Sep 46