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C R Triggle

Publications and source records attributed to C R Triggle.

117 records · Page 7Linked to original sources
PubMed1975

The action of the ionophores, X-537A and A-23187, on smooth muscle.

The cation ionophore X-537A in the concentration range of 10(-6) to 3 X 10(-5) M produced contractions in the rat and guinea-pig vas deferens. No contractile effect was produced in either of the vasa deferentia preparations by the ionophore A-23187 in the concentration range of 10(-7) to 5 X 10(-5) M. In contrast, X-537A had no contractile effect on the guinea-pig ileal longitudinal smooth muscle while A-23187 produced a dose and [Ca2+] dependent contraction. The contractile effect of X-537A in the vasa deferentia preparations is abolished by phenoxybenzamine or prior reserpine treatment and is therefore attributed to the release of norepinephrine. The effect of A-23187 in the intestinal smooth muslce is attributed to a direct Ca2+ transporting action since its contractile effect is unaffected by histamine, acetylcholine, or 5-hydroxytryptamine antagonists.

Animals↗
PubMed1975

Intestinal smooth muscle contraction and the effects of cadmium and A23187.

Pretreatment of the guinea-pig ileal longitudinal muscle preparation with cadmium (Cd++) in the concentration range 5 to 1000 muM resulted in an inhibition of the phasic and tonic contractions induced by both high potassium and the muscarinic agonist, cis-2-methyl-4-dimethylaminomethyl-1,3-dioxolane methiodide. The K+ contracture was significantly more sensitive to the inhibitory action of Cd++ in the concentration range 5 to 100 muM, but not at concentrations of Cd++ above 100 muM. Low concentrations of Cd++, 0.1 to 0.01 muM, were found to increase by an atropine-sensitive mechanism, the spontaneous activity of approximately 50% of the preparations tested. It was also shown that the ionophore A23187 produced a concentration-dependent contraction in the guinea-pig ileal longitudinal muscle that was dependent upon the presence of extracellular calcium. When 1.8 mM Cd++ was added to a tissue that had been incubated in Ca++-free media for 60 minutes and pretreated with 5 muM A23187 for 15 minutes, a slow contractile response was recorded. Similar, but significantly smaller, contractions were also recorded when 1.8 mM Ca++, Mn++, Sr++, Pb++ and Ba++, but not when Co++, Ni++, Hg++, UO2++, and Tm++ and Th++++ were administered. It was concluded that the contractile action of these cations was dependent on ionic radius, hydration energy, valency and, perhaps, coordination number, and was due to the intracellular entry of the cation where it resulted in the release of bound Ca++ and/or directly activated the smooth muscle troponin system.

Animals↗
PubMedDate not supplied

Novel endothelium-derived relaxing factors. Identification of factors and cellular targets.

Nitric oxide (NO), together with prostacyclin (PGI2), mediates shear stress and endothelium-dependent vasodilator-mediated vasorelaxation. In the presence of inhibition of NO synthase (NOS) with nitroarginine analogues, such as of N(w)-nitro-L-arginine methyl ester (L-NAME) and N(w)-nitro-L-arginine (L-NNA), and indomethacin, to inhibit cyclooxygenase (COX) and the synthesis of PGI2, many blood vessels still respond with an endothelium-dependent relaxation to either chemical [i.e. acetylcholine (ACh)] or mechanical (shear stress) activation. This non-NO and non-PGI2 vasorelaxation appears to be mediated by hyperpolarization of the vascular smooth muscle cell (VSMC). Although NO can hyperpolarize VSMC, a novel mediator, the endothelium-derived hyperpolarizing factor (EDHF), which opens a VSMC K(+) channel(s) notably in resistance vessels, has been proposed. Little agreement exists as to the nature of this putative factor, but several candidate molecules have been proposed and evidence, notably from the microcirculation, suggests that endothelium-dependent hyperpolarization (EDH) may be mediated via low electrical resistance coupling via myoendothelial gap junctions. We describe a number of techniques that are being used to identify EDHF and present data that address the contribution of a small increase in extracellular K(+) as an EDHF.

Animals↗
PubMedDate not supplied

Effects of pertussis and cholera toxins on alpha-adrenoceptor function in rat tail artery: differences in hypertension.

The alpha 1- and alpha 2-adrenoceptor-stimulated contractile responses of rat tail artery rings were compared in Sprague-Dawley (SD), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY) rats that were untreated, treated with pertussis toxin, or treated with cholera toxin. The maximal responses, expressed as milligrams of tension, induced by clonidine (an alpha 2-adrenoceptor agonist) and cirazoline (a selective alpha 1-adrenoceptor agonist) were significantly greater in SHR than in SD or WKY, and the tissues were more sensitive to the agonists in SHR or SD than in WKY. Yohimbine (0.1 microM), a selective alpha 2-adrenoceptor antagonist, shifted the dose-response curves for clonidine to the right. The effects of yohimbine were greater in SD than in WKY or SHR, but not different between WKY and SHR. Prazosin (0.05 microM), a selective alpha 1-adrenoceptor antagonist, shifted the dose-response curves of cirazoline to the right, but the effects of prazosin were not different among these three strains of rats. Nifedipine (0.05 microM) completely blocked the response to clonidine in SD and WKY; however, in SHR, approximately one-third of the response to clonidine was resistant to nifedipine. Nifedipine, at 0.05 microM, only partially inhibited responses to cirazoline in SD, SHR, and WKY, and no differences were noted between the strains. Pertussis toxin pretreatment (50 micrograms/kg, 3 days before experiment) almost completely blocked the responses to clonidine, but only partially inhibited those to cirazoline. After pertussis toxin pretreatment, the responses (maximal effects and EC50s) to clonidine and cirazoline were not significantly different in arteries from the three strains of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-1 Receptor Antagonists↗
PubMedDate not supplied

Endothelium-independent relaxations to acetylcholine and A23187 in the human umbilical artery.

The effects of acetylcholine (ACh) and A23187 on ring preparations from the human umbilical artery (HUA) were investigated and compared with the rat aorta (RA). The results from the HUA demonstrate that: (1) At both high (pO2 > 600 mm Hg) and low O2 tension (pO2 < 55 mm Hg), ACh and A23187 relaxed precontracted rings in a concentration-dependent and endothelium-independent manner. Changes in pO2 did not influence the responses of the HUA to either relaxant. (2) Relaxation responses of the HUA to either ACh or A23187 were insensitive to methylene blue (50 microM), L-nitro-arginine methyl ester (100 microM), indomethacin (10 microM) and nordihydroguaiaretic acid (50 microM). Relaxations initiated by ACh were also atropine-resistant. (3) Meclofenamic acid (3 microM) suppressed the relaxations to A23187, but not ACh. (4) Regardless of pO2 superoxide dismutase (100 U/ml) potentiated the relaxant effects of ACh, whereas mannitol (60 mM) enhanced ACh-initiated relaxations at high but not low pO2. (5) Ouabain (30 nM), high potassium (HK+, 60 mM) and tetraethylammonium (20 mM) inhibited responses to ACh. (6) Na(+)-free physiological saline solution inhibited both relaxations and oscillations initiated by either ACh or A23187. (7) Both nitroglycerin and exogenous nitric oxide (NO) fully, and 8-bromoguanosine 3',5'-cyclic monophosphate partially, relaxed the HUA, and LY83583 (10 microM) reversed such relaxations. (8) In the RA, relaxation responses to ACh and A23187 were endothelium-dependent and sensitivity was reduced under high versus low pO2 conditions. We conclude that in the HUA, unlike in the RA, ACh and A23187 mediate their responses via an endothelium- and NO-independent process(es), perhaps involving the release of a muscle-derived relaxing factor. ACh-initiated relaxations are mediated by activation of Na+,K(+)-ATPase, and subsequent hyperpolarization via K+ efflux, whereas A23187-mediated relaxations result from the synthesis of an indomethacin-resistant cyclooxygenase product.

Acetylcholine↗
PubMedDate not supplied

Cardiac hypertrophy in experimental hypertension: interaction of the sodium ion, blood pressure and lisinopril.

The interaction of blood pressure, salt intake and the inhibition of angiotensin converting enzyme activity with cardiac hypertrophy were examined in the Dahl rat model. Eight-week-old salt sensitive and salt resistant rats were each separated into two colonies, one of which was maintained on a low salt and the other on a high salt diet for three weeks, at the end of which time both salt sensitive colonies were hypertensive. Each colony was then separated into two groups, one received no medication the other was given lisinopril until normotension was achieved. After 11 weeks of therapy, intra-arterial blood pressures and heart rates were recorded. The rats were sacrificed and heart weight to body weight ratios were determined. Both untreated salt sensitive groups displayed marked cardiac hypertrophy which correlated well with diastolic blood pressure irrespective of salt intake. Lisinopril therapy lowered blood pressures to normotensive levels in all groups except for salt sensitive rats ingesting a high salt diet where, despite a 10-fold increase in drug dose, normotension was not achieved. Significant cardiac regression accompanied lisinopril therapy in rats receiving low salt diets but high salt intake severely attenuated regression in both strains. There was no significant correlation between heart weight and blood pressure in the treated groups. The results suggest that cardiac regression appears to be mediated by other factors besides ventricular afterload pressure and that high salt intake adversely affects blood pressure and heart weight response to lisinopril therapy.

Angiotensin-Converting Enzyme Inhibitors↗