Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The radioactive microsphere technique was used to study hemodynamic mechanisms of action of 2 calcium antagonists--foridon and nifedipine in conscious rabbits with acute hypertension evoked by immobilization. Microspheres were injected before and 5 min after bolus i.v. injection of equihypotensive (10% blood pressure drop) doses of nifedipine (30 mcg/kg) and foridon (50 mcg/kg). Nifedipine in most cases decreased cardiac index by 7% without significant changes in regional hemodynamic. After foridon injection total peripheral resistance decreased by 19% (P less than 0.05) and cardiac index increased by 18%. There were increase in blood flow: in the heart by 34% (P less than 0.05), in the skeletal muscle by 41% (P less than 0.05) and in testes by 12% (P less than 0.05). The results show that in acute stress-induced hypertension these dihydropyridine-derivatives have different hemodynamic mechanisms of action: nifedipine preferentially depress myocardial contractility, whereas foridon dilates blood vessels.
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PMID:[Hemodynamic mechanisms of the hypotensive action of the new calcium antagonist foridon in acute hypertension in rabbits. A comparison with nifedipine]. 380 Nov 31

We studied wild-type (WT) and Cav1.3(-/-) mouse chromaffin cells (MCCs) with the aim to determine the isoform of L-type Ca(2+) channel (LTCC) and BK channels that underlie the pacemaker current controlling spontaneous firing. Most WT-MCCs (80%) were spontaneously active (1.5 Hz) and highly sensitive to nifedipine and BayK-8644 (1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-3-pyridinecarboxylic acid, methyl ester). Nifedipine blocked the firing, whereas BayK-8644 increased threefold the firing rate. The two dihydropyridines and the BK channel blocker paxilline altered the shape of action potentials (APs), suggesting close coupling of LTCCs to BK channels. WT-MCCs expressed equal fractions of functionally active Cav1.2 and Cav1.3 channels. Cav1.3 channel deficiency decreased the number of normally firing MCCs (30%; 2.0 Hz), suggesting a critical role of these channels on firing, which derived from their slow inactivation rate, sizeable activation at subthreshold potentials, and close coupling to fast inactivating BK channels as determined by using EGTA and BAPTA Ca(2+) buffering. By means of the action potential clamp, in TTX-treated WT-MCCs, we found that the interpulse pacemaker current was always net inward and dominated by LTCCs. Fast inactivating and non-inactivating BK currents sustained mainly the afterhyperpolarization of the short APs (2-3 ms) and only partially the pacemaker current during the long interspike (300-500 ms). Deletion of Cav1.3 channels reduced drastically the inward Ca(2+) current and the corresponding Ca(2+)-activated BK current during spikes. Our data highlight the role of Cav1.3, and to a minor degree of Cav1.2, as subthreshold pacemaker channels in MCCs and open new interesting features about their role in the control of firing and catecholamine secretion at rest and during sustained stimulations matching acute stress.
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PMID:Loss of Cav1.3 channels reveals the critical role of L-type and BK channel coupling in pacemaking mouse adrenal chromaffin cells. 2007 12