Postsynaptic α-adrenoceptor characterization and Ca2+ channel antagonist and activator actions in rat tail arteries from normotensive and hypertensive animals

1986 ◽  
Vol 64 (7) ◽  
pp. 909-921 ◽  
Author(s):  
C. M. Su ◽  
V. C. Swamy ◽  
D. J. Triggle
Keyword(s):  
Rank Order ◽  
Rat Tail Artery ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Tail Artery ◽  
Mechanical Responses ◽  
Adrenoceptor Agonist ◽  
Adrenoceptor Agonists ◽  
Wistar Kyoto ◽  
Rat Tail

Postsynaptic α-adrenoceptors in the rat tail artery have been examined by determining the pA2 values for antagonists against several α-adrenoceptor agonists. In this tissue the α-adrenoceptor agonists all produce concentration-dependent mechanical responses with the following rank order of potency: clonidine > norepinephrine > phenylephrine > UK 14304 > B-HT 920. Antagonism by prazosin and yohimbine of phenylephrine, norepinephrine, and clonidine responses does not reveal the anticipated discrimination between α1- and α2-adrenoceptors. Thus, pA2 values for prazosin (9.1–9.5), yohimbine (7.2–7.4), and corynanthine (7.0–7.1) and idazoxan (7.6) do not show large differences between these receptor agonists and suggests the predominance of α1-adrenoceptor mediated contractile responses in this preparation. Significant differences between antagonist activities (pA2 values) in Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) artery preparations have not been observed. The sensitivity sequence of α-adrenoceptor agonist-induced responses to nifedipine and D 600 is B-HT 920 > clonidine > phenylephrine > norepinephrine. Dependence of agonist response upon extracellular Ca2+ parallels the sensitivity to Ca2+ channel antagonists. Sensitivity to D 600 of phenylephrine responses increased with decreasing concentration of phenylephrine or with receptor blockade by phenoxybenzamine: sensitivity of responses to B-HT 920 was not affected by these procedures. Tail artery strips from WKY and SHR do not exhibit major differences in sensitivity to D 600 or to Ca2+ depletion. Bay k 8644, a Ca2+ channel activator, produces concentration-dependent mechanical responses in the tail artery in the presence of modestly elevated K+ concentrations (10–15 mM): these actions of elevated K+ can be mimicked by both α1- and α2-adrenoceptor agonists including methoxamine, St 587, UK 14304, and clonidine. These studies do not provide clear evidence for the existence of discrete postsynaptic α1- and α2-adrenoceptor populations in rat tail artery as indicated by pA2 values or Ca2+ dependence of response.

Adrenergic activity in arteries of spontaneously hypertensive rats

1981 ◽  
Vol 59 (10) ◽  
pp. 1104-1107 ◽  
Author(s):  
Thomas T. Zsotér ◽  
Steve Sirko ◽  
Camille Wolchinsky ◽  
Dezso Kadar ◽  
Laszlo Endrenyi
Keyword(s):  
Column Chromatography ◽  
Spontaneously Hypertensive Rats ◽  
Similar Proportion ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Tail Artery ◽  
Wistar Kyoto Rats ◽  
Adrenergic Activity ◽  
Wistar Kyoto ◽  
Uptake And Release

This study compares the uptake and release of [3H]norepinephrine and residual 3H content in the tail artery of 7- to 9-week-old and 16- to 18-week-old spontaneously hypertensive rats (SHR) and age matched normotensive Wistar Kyoto rats (WKR). The composition of the 3H overflow from the artery, analyzed with column chromatography, revealed similar proportion of norepinephrine and in metabolites, namely normetanephrine, O-methylated deaminated products, dihydroxy-phenylglycol, and dihydroxymandelic acid in SHR and WKR. [3H]Norepinephrine was retained however in greater proportion in vessels of young and older SHR than in WKR.

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

1993 ◽  
Vol 71 (10-11) ◽  
pp. 791-799 ◽  
Author(s):  
Xiao-Fang Li ◽  
Christopher R. Triggle
Keyword(s):  
Cholera Toxin ◽  
Pertussis Toxin ◽  
Rat Tail Artery ◽  
Response Curves ◽  
Contractile Responses ◽  
Tail Artery ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
The Right ◽  
Rat Tail

The α1- and α2-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 α2-adrenoceptor agonist) and cirazoline (a selective (α1-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 μM), a selective α2-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 μM), a selective α1-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 μM) 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 μM, only partially inhibited responses to cirazoline in SD, SHR, and WKY, and no differences were noted between the strains. Pertussis toxin pretreatment (50 μg/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. A combination of pertussis toxin and nifedipine resulted in an additive inhibition of the responses induced by cirazoline. cholera toxin pretreatment (0.3 mg/kg, 3 days before experiment), however, had no effects on the contractile responses induced by either clonidine or cirazoline, or on the inhibitory effects of nifedipine in SHR, SD, and WKY. These results indicate that (i) the maximal responses to α1- and α2-adrenoceptor agonists are enhanced in rat tail artery rings from SHR; (ii) tissues from SH and SD rats are also more sensitive to cirazoline and clonidine than are tissues from WKY; (iii) responses to clonidine, but not cirazoline, in tissues from the SHR are less sensitive to nifedipine than tissues from SD and WKY; (iv) a G-protein sensitive to pertussis but not cholera toxin is involved in the regulation of both α1 and α2-adrenoceptor signal transduction processes in rat tail artery smooth muscle; and (v) pretreatment with pertussis toxin reduces the enhanced response levels of SHR tissues so that the maximal contractile responses to both α1- and α2-adrenoceptor agonists are equivalent in arteries from the three strains of rats.Key words: pertussis toxin, cholera toxin, α1-adrenoceptor, α2-adrenoceptor, rat tail artery ring.

Calcium channel activation in vascular smooth muscle by BAY K 8644

1984 ◽  
Vol 62 (11) ◽  
pp. 1401-1410 ◽  
Author(s):  
C. M. Su ◽  
V. C. Swamy ◽  
D. J. Triggle
Keyword(s):  
Smooth Muscle ◽  
Dose Response ◽  
Response Curve ◽  
Bay K 8644 ◽  
Rat Tail Artery ◽  
Channel Activation ◽  
Tail Artery ◽  
Voltage Dependent ◽  
Adrenoceptor Agonists ◽  
Rat Tail

BAY K 8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate) and CGP 28 392 (ethyl-4(2-difluoromethoxyphenyl)-1,4,5,7-tetrahydro-2-methyl-5-oxofuro-[3,4-b]pyridine-3-carboxylate) are closely related in structure to nifedipine and other 1,4-dihydropyridine Ca2+ channel antagonists. However, both BAY K 8644 and CGP 28 392 serve as activators of Ca2+ channels. In the rat tail artery, responses to BAY K 8644 are dependent upon [Formula: see text] and prior stimulation by K+ or by the α-adrenoceptor agonists, phenylephrine and BHT 920 (6-allyl-2-amino-5,6,7,8,-tetrahydro-4H-thiazolo[4,5-d]azepin dihydrochloride). Responses are blocked noncompetitively by the Ca2+ channel antagonists D-600 ((−)-D-600 > (+)-D-600) and diltiazem, but competitively by nifedipine (pA2 = 8.27). This suggests that activator and inhibitor 1,4-dihydropyridines interact at the same site. BAY K 8644 potentiates K+ responses and Ca2+ responses in K+-depolarizing media. The leftward shift of the K+ dose–response curve produced by BAY K 8644 suggests that this ligand facilitates the voltage-dependent activation of the Ca2+ channel. The pA2 value for nifedipine antagonism of BAY K 8644 responses is significantly lower than that for nifedipine antagonism of Ca2+ responses in K+ (25–80 mM) depolarizing media (9.4–9.6), suggesting that the state of the channel may differ according to the activating stimulus.

Slow and incomplete sympathetic reinnervation of rat tail artery restores the amplitude of nerve-evoked contractions provided a perivascular plexus is present

2011 ◽  
Vol 300 (2) ◽  
pp. H541-H554 ◽  
Author(s):  
Diana Tripovic ◽  
Svetlana Pianova ◽  
Elspeth M. McLachlan ◽  
James A. Brock
Keyword(s):  
Rat Tail Artery ◽  
Adult Rats ◽  
Tail Artery ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Perivascular Plexus ◽  
Evoked Contractions ◽  
Comparable Amplitude ◽  
Rat Tail

We have investigated the recovery of sympathetic control following reinnervation of denervated rat tail arteries by relating the reappearance of noradrenergic terminals to the amplitude of nerve-evoked contractions of isometrically mounted artery segments in vitro. We have also assessed reactivity to vasoconstrictor agonists. Freezing the collector nerves near the base of the tail in adult rats denervated the artery from ∼40 mm along the tail. Restoration of the perivascular plexus declined along the length of the tail, remaining incomplete for >6 mo. After 4 mo, nerve-evoked contractions were prolonged but of comparable amplitude to control at ∼60 mm along the tail; they were smaller at ∼110 mm. At ∼60 mm, facilitation of contractions to short trains of stimuli by the norepinephrine transporter blocker, desmethylimipramine, and by the α2-adrenoceptor antagonist, idazoxan, was reduced in reinnervated arteries. Blockade of nerve-evoked contractions by the α1-adrenoceptor antagonist, prazosin, was less and by idazoxan greater than control after 8 wk but similar to control after 16 wk. Sensitivity of reinnervated arteries to the α1-adrenoceptor agonist, phenylephrine, was raised in the absence but not in the presence of desmethylimipramine. Sensitivity to the α2-adrenoceptor agonist, clonidine, was maintained in 16-wk reinnervated arteries when it had declined in controls. Thus regenerating sympathetic axons have a limited capacity to reinnervate the rat tail artery, but nerve-evoked contractions match control once a relatively sparse perivascular plexus is reestablished. Functional recovery involves prolongation of contractions and deficits in both clearance of released norepinephrine and autoinhibition of norepinephrine release.

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