Effects of Angiotensin Ii and 1-Sar., 8-Isoleu. Angiotensin Ii on Electrical and Mechanical Properties of the Portal Vein From Rats of Different Ages

The possible involvement of a GTP-binding protein in the regulation of Ca2+ channels by angiotensin II (Ang II) in vascular muscle cells was investigated by the whole-cell voltage-clamp method. Single cells were freshly isolated from guinea pig portal vein. The pipette solution contained high Cs+ to inhibit K+ currents and thereby isolate the Ca2+ channel current. Ba2+ (2 mM) was in the bath solution as a charge carrier for the Ca2+ channel. Application of Ang II (0.1-100 nM) produced an increase in peak amplitude of the Ba2+ current, with a shift of the current-voltage curve in the negative direction. These effects were inhibited by pretreatment with an antagonist of the Ang II receptor, [Sar1,Ile8]-Ang II. Presence of 0.1 mM GTP in the pipette solution stabilized the Ang II action, but 0.3-1.0 mM GDP-beta-S and 1.0 mM GTP-gamma-S inhibited it. GTP-gamma-S alone produced a slowly progressing increase in the basal (unstimulated) current amplitude. Preincubation of muscle tissues with pertussis toxin (1 micrograms/ml, for up to 6 hours at 36 degrees C) or intracellular application of preactivated pertussis toxin (1 micrograms/ml) plus NAD (1 mM) did not inhibit the Ang II action. Cholera toxin (10 micrograms/ml) also had no effect on the Ang II action. These results suggest that the Ang II stimulation of Ca2+ channels in smooth muscle of guinea pig portal vein may be mediated by a G protein that is insensitive to both pertussis toxin and cholera toxin.

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Exaggerated Hypotensive Responses to Calcium Antagonists in Spontaneously Hypertensive Rats

Takata

Hutchinson

1983

Clinical and Experimental Hypertension. Part A: Theory and Prac

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The hypotensive effects of intravenous injection and infusion of diltiazem, l- and d-verapamil were investigated in conscious and anaesthetized rats with spontaneous hypertension (SHR) and normal blood pressure (NT-WKY). The inhibitory actions of these calcium-influx blockers on the pressor responses to angiotensin II (AII) and noradrenaline (NA) were also examined in anaesthetized SHR and NT-WKY. The intravenous injections of these three drugs (0.03, 0.1, 0.3, 1.0 mg/kg) lowered mean arterial pressure (MAP) in a dose related manner in conscious NT-WKY and SHR. The small dose of the blockers administered by intravenous infusion (0.02 mg/kg per min) also decreased MAP in both groups. The potency of the antihypertensive action was in the order l-verapamil greater than d-verapamil = diltiazem. The fall in blood pressure expressed as percentage of the initial MAP produced by the compounds was significantly enhanced in SHR compared to NT-WKY. The pressor responses to AII (0.03, 0.1, 0.3, 1.0 micrograms/kg i.v.) were suppressed by the intravenous infusion of 20 micrograms/kg per min with l-verapamil but not with d-verapamil, diltiazem and vehicle in NT-WKY, while no calcium blocker significantly diminished the vasopressor action of AII in SHR. The pressor effects of NA (0.3, 1.0, 3.0, 10.0 micrograms/kg i.v.) were inhibited by the same doses of l-verapamil and diltiazem but not with d-verapamil and vehicle in NT-WKY. Diltiazem reduced the response to NA in SHR but the other compounds (l- and d-verapamil) did not alter the pressor response to NA in SHR. The pressor responses to arginine vasopressin (3, 10, 30 and 100 mU/kg i.v.) were not altered by diltiazem infusion in either SHR or NT-WKY. It is concluded that these compounds are different in the potency of their hypotensive action and also the inhibition of the pressor responses to AII and NA. Calcium entry blockers are more effective antihypertensive agents in SHR than in NT-WKY. It appears that their inhibitory effects on the responses to AII and NA do not explain the exaggerated hypotensive responses in SHR.

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Effects of Angiotensin Ii and 1-Sar., 8-Isoleu. Angiotensin Ii on Electrical and Mechanical Properties of the Portal Vein From Rats of Different Ages

Cited by 3 publications

References 13 publications

Electrophysiology of Vascular Smooth Muscle

Electrophysiology of Vascular Smooth Muscle

Involvement of a GTP-binding protein in stimulating action of angiotensin II on calcium channels in vascular smooth muscle cells.

Exaggerated Hypotensive Responses to Calcium Antagonists in Spontaneously Hypertensive Rats

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