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C R Triggle

Publications and source records attributed to C R Triggle.

At least 109 records · Page 6Linked to original sources
PubMed1984

Systolic blood pressure responses to enalapril maleate (MK 421, an angiotensin converting enzyme inhibitor) and hydrochlorothiazide in conscious Dahl salt-sensitive and salt-resistant rats.

Systolic blood pressure responses to enalapril maleate (MK 421, a new angiotensin converting enzyme inhibitor (CEI] and hydrochlorothiazide (HTZ) were studied in conscious Dahl salt-sensitive (DS) and salt-resistant (DR) rats maintained on a high salt (8.0% NaCl) and a normal salt (0.4% NaCl) diet. The DS rats were severely hypertensive after 3 weeks on the high salt diet whereas the systolic blood pressure (SBP) of the DR rats were normotensive. Oral treatment with enalapril (15-100 mg X kg-1 X day-1) and HTZ (60-400 mg X kg-1 X day-1) caused a significant reduction of SBP in the DS rats with the high salt diet (P less than 0.001); however, this was not observed until after 4 weeks of treatment when the dosage was 30 and 150 mg X kg-1 X day-1, respectively. Furthermore, enalapril therapy alone significantly reduced the SBP of all groups of rats regardless of diet or Dahl strain (P less than 0.001), but this was not observed until the end of the 7th week of therapy in DR rats on 8.0% NaCl and the end of the 3rd week of therapy for DR and DS rats on 0.4% NaCl. These results suggest that enalapril may lower SBP by mechanisms other than those related to an action as a CEI.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Specific high affinity binding of the calcium channel antagonist, [3H]nitrendipine, to rat liver microsomes.

Some key properties of the binding of [3H]nitrendipine, an analogue of the 1,4-dihydropyridine, nifedipine, to a plasma membrane enriched microsomal fraction from the rat liver are described. Specific binding was saturable, linear with protein concentration, and reversible. The apparent equilibrium dissociation constant, KD, was 4.20 +/- 0.22 nM and the maximum density of binding, Bmax, was 3.02 +/- 0.17 pmol/mg of protein determined from Scatchard analysis of binding at 10 degrees C. Inhibition of binding was specific for dihydropyridines with competitive inhibition being noted with nifedipine and 4-chloronifedipine, as well as BAY K-8644, a calcium channel agonist. A biphasic displacement curve was recorded for methoxy verapamil (D-600), and a triphasic competition curve with lanthanum (La3+), and diltiazem demonstrated competitive kinetics. The high affinity binding site for nitrendipine in the liver, although having some similar properties to those sites described in skeletal muscle, would appear to be distinctive with respect to its unique sensitivity to D-600 and diltiazem. We speculate that this binding site may represent a Ca2+ channel responsible for regulating Ca2+ influx and hepatic glycogenolysis.

Animals↗
PubMed1984

The reversal of left ventricular hypertrophy with control of blood pressure in experimental hypertension.

The precise mechanisms of hypertensive left ventricular hypertrophy and reversal with antihypertensive drugs are unclear and complex. Enalapril maleate (MK421) and hydrochlorothiazide (HTZ) were used to assess the control of hypertension, and reversal of left ventricular hypertrophy in Dahl sensitive (DS) and Dahl resistant (DR) rats given either a high (8% NaCl), or a low (0.4% NaCl) salt diet. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), left ventricular weight/body weight (LVwt/Bwt) ratio were determined. Both drugs were effective in reducing blood pressure and left ventricular mass in DS rats placed on a high salt diet. For DR rats under the same conditions, only MK421 induced significant lowering of blood pressure. Neither drug caused significant change in ventricular mass. Both DS and DR rats on a low salt diet underwent significant blood pressure reduction with MK421 but not HTZ. Significant regression of the left ventricle was observed only in DS rats treated with MK421. Regression was not observed in DR rats even though MK421 reduced blood pressure to distinctly hypotensive levels. The dissociation of left ventricular mass and blood pressure control observed with both MK421 and HTZ suggests that pressure afterload is not the only factor involved in the pathophysiology of hypertensive cardiac hypertrophy. The mechanisms of anti-hypertensive drug action and salt intake both appear to play a significant if unexplained role.

Animals↗
PubMed1984

Pharmacological characterization of the postsynaptic alpha adrenoceptors in vascular smooth muscle from canine and rat mesenteric vascular beds.

Postsynaptic alpha adrenoceptors have been characterized in rat superior mesenteric artery and branches of canine mesenteric artery. l-Phenylephrine, naphazoline and clonidine were used as agonists and prazosin and yohimbine were used as antagonists. The pA2 values for prazosin and yohimbine were determined against these agonists in canine and rat mesenteric arteries. The pA2 values for either prazosin or yohimbine were similar when l-phenylephrine and naphazoline were used as the agonists. The slope of the Schild plot was less than unity for prazosin and yohimbine acting as antagonists to l-phenylephrine in canine mesenteric artery whereas in the rat mesenteric artery, the slopes obtained for either phenylephrine or naphazoline against the antagonists were not significantly different from unity. In rat mesenteric artery, the pA2 value for yohimbine against clonidine was not statistically different from values obtained with the other agonists; however, in the presence of prazosin the dose-response curve to clonidine was biphasic, suggesting that the action of clonidine is mediated through two distinct sites to which prazosin has different affinities. However, these results do not provide definitive support for the concept of functionally independent subtypes of postsynaptic alpha adrenoceptors in rat and canine mesenteric artery.

Animals↗
PubMed1983

An analytical approach to the preparation and characterization of subcellular membranes from canine mesenteric arteries.

Subcellular membrane fractions were isolated from dog mesenteric arteries by differential and isopynic sucrose density gradient centrifugations. Isolated membrane fractions were characterized by marker enzyme activities, morphological features and sodium dodecyl sulfate-polyacrylamide gel electrophoretic patterns. Our results show that the microsomal fraction isolated by conventional differential centrifugation was highly heterogenous and contained substantial amount of plasma membranes which could be further enriched as a light density membrane fraction on a discontinuous sucrose density gradient. The microsomal fraction and its subfractions were vesicular in appearance under electron microscope and were capable of binding and actively transporting Ca2+. The binding of Ca2+ and ATP-supported Ca2+-transport in the presence or absence of oxalate paralleled the distribution of plasma membrane marker enzyme activities suggesting that plasma membranes in vascular smooth muscle may play a major role in handling Ca2+ and thus the control of contractile function.

Adenosine Triphosphate↗
PubMed1983

Cardiac regression and blood pressure control in the Dahl rat treated with either enalapril maleate (MK 421, an angiotensin converting enzyme inhibitor) or hydrochlorothiazide.

Enalapril maleate (MK 421), and hydrochlorothiazide were used to evaluate the control of hypertension and reversal of myocardial hypertrophy in Dahl sensitive (DS) and Dahl resistant (DR) rats given either a high (8% NaCl) or a low salt (0.4% NaCl) diet. Groups of six-week-old male DS and DR rats were treated with enalapril (15-100 mg/kg/day) in drinking water for eight weeks. Additional comparable groups of DS and DR were also treated with hydrochlorothiazide (60-400 mg/kg/day). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and heart weight/body weight (Hwt/Bwt) ratio were determined. We observed significant reduction in Hwt/Bwt ratio (P less than 0.001) along with control of SBP and DBP in the DS given a high salt diet treated with either enalapril or hydrochlorothiazide. However, in the DR given a high salt diet, cardiac regression (Hwt/Bwt ratio, P less than 0.05), SBP and DBP (P less than 0.01) reduction were seen only with enalapril. Similarly, cardiac regression (Hwt/Bwt ratio, P less than 0.05) was observed along with reduction of SBP and DBP (P less than 0.001) in the DS given a low salt diet and DR given enalapril. These data indicate that enalapril reduced SBP and DBP in association with cardiac regression in hypertensive and normotensive rats. In contrast, hydrochlorothiazide only reduced SBP, DBP and caused cardiac reversal (Hwt/Bwt ratio) in DS placed on a high salt diet.

Animals↗
PubMed1983

The action of the ionophore ionomycin in guinea-pig intestinal smooth muscle.

The ionophore ionomycin produced concentration-dependent (5 X 10(-9) to 5 X 10(-6) M) contractions in guinea-pig ileal longitudinal smooth muscle. Responses were dependent on extracellular Ca2+, consistent with the known role of this Ca2+ source in supporting excitation-contraction coupling to a variety of stimulants in this tissue. Responses were insensitive to atropine (10(-6) M) but were dependent upon extracellular Na+ and were completely blocked by low concentrations of the Ca2+-channel antagonists nicardipine, YC-93 (5 X 10(-7) M), and D-600 (5 X 10(-6) M). The behaviour of ionomycin is very similar to that shown by A 23187 in this tissue. Ionomycin, like A 23187, can apparently activate D-600 sensitive Ca2+ channels in the guinea-pig intestinal smooth muscle rather than simply translocating Ca2+EXT.

Animals↗
PubMed1983

Regression of left ventricular hypertrophy and control of hypertension in the spontaneously hypertensive rat (SHR): oxprenolol versus hydrochlorothiazide.

The control of hypertension with antihypertensive agents, in the spontaneously hypertensive rats (SHR) can result in regression of established cardiac hypertrophy. This study compared the effects of therapy with oxprenolol (Ox) and with hydrochlorothiazide (Htz) for (1) regression of established left ventricular hypertrophy (LVH) and (2) blood pressure control. Three groups of SHR and 3 comparable groups of Wistar-Kyoto (WKY) rats, matched for age, sex and body wt, were treated with tap water (Gp I), 60-200 mg hydrochlorothiazide kg-1 day-1 (Gp II) and 15-500 mg oxprenolol kg-1 day-1 (Gp III) for 13 weeks. Systolic and diastolic blood pressures (SBP, DBP mmHg), left ventricular wt/body wt ratio (LVwt/Bwt mg g-1) and left ventricular wall thickness (LVWT mm) were recorded. Oxprenolol lowered both systolic (mean +/- S.E. mmHg, 130 +/- 7 vs 189 +/- 8; P less than 0.01) and diastolic blood pressures (mean +/- S.E. mmHg, 104 +/- 6 vs 159 +/- 6; P less than 0.001) and caused regression of left ventricular hypertrophy (mean +/- S.E. mg g-1, 2.91 +/- 0.06 vs 3.10 +/- 0.09; P less than 0.05). In contrast, hydrochlorothiazide did not control blood pressure (mean +/- S.E. mmHg, 183 +/- 5 vs 189 +/- 6 and 152 +/- 5 vs 156 +/- 6), but it did cause regression of left ventricular hypertrophy (mean +/- S.E. mg g-1, 2.67 +/- 0.03 vs 3.10 +/- 0.09; P less than 0.01). Left ventricular wall thickness, measured in the mid-ventricular region, was significantly reduced only by hydrochlorothiazide (mean +/- S.E. mm, 2.76 +/- 0.06 vs 3.21 +/- 0.01; P less than 0.05). These results suggest that regression of left ventricular hypertrophy can occur with or without control of hypertension in the SHR.

Animals↗
PubMed1983

On the oxalate stimulation of ATP-dependent calcium accumulation by smooth muscle subcellular membranes.

Subcellular distribution of azide-insensitive, ATP-dependent Ca -accumulation in the presence and absence of 5 mM oxalate by fractions isolated from several different types of smooth muscle were studied. Although oxalate stimulated the Ca -accumulation to various degrees depending upon the source of smooth muscle used, there was no clear association between the stimulatory effect of oxalate and the distribution of any of the enzyme activities used as markers for various membranes. The distribution of ATP-dependent Ca -accumulation in the absence of oxalate, on the other hand, correlates relatively well with that of the plasma membrane marker in spite of reduced total recovery of the Ca -accumulation compared to those of the protein content and membrane markers. However, a greater reduction in the total percent recovery of the ATP-dependent Ca accumulation by fraction from three different types of smooth muscle was consistently observed when carried out in the presence compared to the absence of oxalate. The discrepancy in the total percent recovery of the Ca -accumulation in the presence and absence of oxalate poses a major concern on the uses of oxalate stimulated, ATP-dependent Ca accumulations as a subcellular membrane marker.

Adenosine Triphosphate↗
PubMed1982

Calcium-channel antagonist binding to isolated vascular smooth muscle membranes.

The binding characteristics of the calcium-channel antagonist nitrendipine, an analog of nifedipine, have been measured in plasma membrane enriched microsomal fractions from the canine thoracic aorta, canine mesenteric artery, and rat mesenteric artery. The dissociation constants, KD, for the high-affinity binding sites were, respectively, 0.308, 0.254, and 0.101 nM and Bmax values for binding capacity were 20.3, 25.0, and 18.0 fmol/mg of microsomal protein. Studies with isolated tissues, in which the sensitivity of the high potassium mechanical response to nitrendipine was determined, indicate that the apparent KD for nitrendipine in the canine mesenteric artery, as reflected by the IC50 (mean inhibition constant) value, is 4.5-5.3 nM and for the rat mesenteric artery 2.5-6.6 nM.

Animals↗
PubMed1982

Chloride removal selectively inhibits phasic contractions of guinea pig ileal longitudinal smooth muscle.

Removal of external chloride selectively and reversibly inhibits the phasic responses of the guinea pig ileal longitudinal muscle to high potassium and cholinergic stimulation. The binding of calcium to a relatively superficial pool is affected by chloride removal. Alterations in anionic composition of bathing solution affects the availability of calcium for excitation--contraction (E--C) coupling in smooth muscle.

Animals↗
PubMed1979

Calcium antagonists and contractile responses in rat vas deferens and guinea pig ileal smooth muscle.

The effect of depletion of extracellular Ca2+ (Ca2+ext) on the loss of responsiveness of the guinea pig ileal longitudinal muscle (g.p.i.l.m.) and the rat vas deferens (r.v.d.) to K+ and cis-2-methyl-4-dimethylaminomethyl-1,3-dioxolane methiodide (CD), and K+ and noradrenaline (NA), has been examined and compared with the effects of a variety of local anesthetics and calcium antagonists. The results indicate that qualitative similarities are apparent with respect to the dependence of agonist-induced activity on Ca2+ext in both the g.p.i.l.m. and r.v.d. Distinct differences, however, in the Ca2+ translocation processes in these two tissues, in response to the different agonists, can be shown by the use of a variety of 'calcium antagonists' thus indicating that such translocation processes are both tissue and agonist selective. It is thus noted that, contrary to the Ca2+ depletion studies, D 600 and the usually more potent BAY-1040 showed no discrimination of action or potency in their ability to inhibit components of the NA response in the r.v.d. In contrast, D 600 and the more potent BAY-1040 selectively inhibited the tonic component of the K+ response. Treatment with SKF 525A and parethoxycaine (PC) in the g.p.i.l.m. and SKF 525A in the r.v.d. resulted in a nonselective inhibition of responses of the tissues to all stimulants. However, in the r.v.d. PC potentiated NA action, and its methobromide (MeBr) derivative potentiated both NA and K+ action and also, like PC, partially shifted to the left the dose-response curve to Ca2+ in NA-depolarizing Ca-free Tyrode's. The quaternary MeBr and the tertiary 2-chloroethyl (2Cl) derivatives of SKF 525A and PC were selectively more effective against CD- than K+ supported contractile activity in the g.p.i.l.m. and the 2Cl derivatives were more effective against NA than K+ responses in the r.v.d. The 2Cl derivative of PC also was more effective in antagonizing the Ca2+ dose-response curve in high-CD or high-NA than in high-K+ Ca2+-free Tyrode's.

Animals↗
PubMed1978

Elevated vascular reactivity in the timolol-treated spontaneously hypertensive rat.

Spontaneously hypertensive rats (SHR) treated in utero with a low dose, and from weaning with 6 mg/kg per day of oral timolol, a noncardioselective beta-adrenergic blocker, did not develop hypertension. Isolated aortic rings from these animals showed increased reactivity to raised extracellular K+, when compared with tissues from timolol-treated Kyoto-Wistar (WKY) control rats. The normotensive SHR aorta also showed significant responsiveness to H+ and to high Ca2+ concentrations without previously depolarizing the tissue with high K+. These observations suggest that the increased reactivity seen in vascular smooth muscle from this animal does not develop secondary to elevated peripheral resistance and subsequent hypertrophy, and that the initiation of hypertension in this animal may be related to a membrane defect and (or) cellular defect which results in a facilitation of Ca2+ availability for the contractile proteins of the SHR vascular smooth muscle cell.

Animals↗
PubMed1977

An analysis of the action of lanthanum on aortic tissue from normotensive and spontaneously hypertensive rats.

Significant tension development resulting from the administration of lanthanum salts (La3+) to isolated aorta tissues was observed in preparations from the spontaneously hypertensive rat (SHR) but not in preparation from age-matched normotensive Wistar rats (NWR). The response to La3+ was significantly greater in tissues maintained in bicarbonate-buffered Krebs than observed in bicarbonate and phosphate-free HEPES-buffered Krebs. At least part of the LA3+ response in the bicarbonate- and phosphate-buffered solutions was due to a pH shift and could be mimicked by raising the extracellular hydrogen ion [H+] concentration. However, a direct action of La3+ on excitation-contraction coupling could be observed in HEPES-buffered solutions where the addition of La3+ also resulted in tension development but no significant pH change; this action of La3+ was found to be resistant to inhibition by maintenance in a Ca2+-free medium and (or) D-600 pretreatment suggesting an intracellular action for La3+. The paradoxical response to both H+ and La3+ in the SHR aorta suggests that the muscle membrane may be more permeable to these ions and, in addition, suggests that the membrane and (or) intracellular calcium stores in this tissue may also be more labile than those in the normotensive controls.

Animals↗
PubMed1976

An analysis of the action of cations of the lanthanide series on the mechanical responses of guinea-pig ileal longitudinal muscle.

1. The inhibitory effects of lanthanide cations (Ln3+) on mechanical responses and 45Ca uptake in guinea-pig ileal longitudinal smooth muscle were studied. 2. Ln3+ strongly inhibited the phasic and tonic component of the response to the muscarinic agonist cis-2-methyl-4-dimethylaminomethyl-1,3-dioxolane methiodide (CD) the two components being affected to the same extent. Inhibition was also obtained for the responses evoked by high K+ but here the effect was mainly on the phasic response, the tonic component was merely delayed. 3. Other members of the Ln3+ series, with the exception of cerium, were found to be more effective than lanthanum in their ability to inhibit the CD response. Thulium, Tm3+, the thirteenth member of the series was the most effective cation. 4. Analysis of 170Tm uptake revealed at least two components. The concentration-dependence of one component, saturating at 2-5 x 10(-6) Tm, corresponded closely to that of the inhibitory effect of Tm3+ on contraction. 5. 170Tm uptake as a function of time showed a secondary rise after 30 min of exposure to the lanthanide. 6. Although 2-5 x 10(-6) M-Tm3+ produced 90% inhibition of the CD and the high K+ induced responses significant reduction of 45Ca uptake by the muscle was only detected when much higher Tm3+ concentrations (greater than or equal 10(-3) M-Tm3+) were used. 7. It is concluded that Ln3+ combine with membrane sites specifically involved in Ca2+ translocation during excitation-contraction coupling.

Animals↗
PubMed1976

The effects of lanthanum and thulium on the mechanical responses of rat vas deferens.

1. The contractile responses of rat vas deferens to noradrenaline and K+ are composed of phasic and tonic components both of which are dependent upon the concentration of extracellular Ca2+. 2. Lanthanum, La3+, and thulium ions, Tm3+, inhibited the noradrenaline and K+ induced responses, complete inhibition being obtained at approximately 10(-3) M-Ln3+. 3. La3+ and Tm3+ were equally effective in inhibiting noradrenaline and K+ responses. The phasic and tonic components of the noradrenaline response were equally sensitive to lanthanide cations, Ln3+, but the phasic component of the K+ response was more sensitive than the tonic component. 4. 170Tm binding did not show any saturable component over the concentration range in which inhibition of the pharmacological response was obtained. 5. It is suggested that the actions of Ln3+ in the rat vas deferens are mediated through some kind of membrane stabilization rather than via a specific Ca2+ binding site concerned with excitation-contraction coupling, the mechanism previously postulated for the Ln3+ action in guinea-pig ileal longitudinal muscle.

Animals↗