Reza Tabrizchi

An improved perfusion apparatus for small animal hearts.

A perfusion apparatus for mechanical and electrophysiological studies in small animal (e.g., rat, guinea pig) hearts is described. The apparatus consists of a number of individual perfusion chambers connected to the aortic perfusion cannula of a Langendorff perfused heart. The aortic root perfusion pressure is controlled by the oxygenating gas (usually 5% CO2 in O2) at a range of 0-200 mmHg. Different solutions can be placed in different individual chambers. Pressure in the left ventricle is monitored by means of a special compliant, but nonelastic, balloon while special atraumatic electrodes allow high-voltage, noise-free ECG recordings to be made from all parts of the epicardium. The apparatus keeps hearts beating for hours while the multichamber allows multiple drug applications to be made rapidly. Thus, the apparatus can be used for all types of pharmacodynamic analysis.

The effects of noradrenaline, B-HT 920, methoxamine, angiotensin II and vasopressin on mean circulatory filling pressure in conscious rats.

1 The effects of vasoactive substances on mean circulatory filling pressure (MCFP), an index of total body venous tone, were determined in conscious rats. 2 Cumulative doses of saline (0.9% w/v NaCl solution), methoxamine (α1‐adrenoceptor agonist), B‐HT 920 (α2‐adrenoceptor agonist) noradrenaline and vasopressin, and individual doses of angiotensin II (AII), were infused into the rats. Mean arterial pressure (MAP), MCFP and heart rate (HR) were determined before and during the plateau responses to infusions of the vasoactive substances. 3 The infusions of all the agonists caused a dose‐dependent increase in MAP and a decrease in HR. The infusion of saline affected neither MAP nor HR. 4 The infusions of saline and methoxamine did not affect MCFP while the infusions of B‐HT 920, noradrenaline and AII increased MCFP. MCFP was slightly increased during the infusion of high doses of vasopressin. 5 It was concluded that receptors for the α2‐adrenoceptor agonist and AII are involved in the control of venous tone. Receptors for the α1‐adrenoceptor agonist and vasopressin are not important for the control of venous tone.

Effects of vasodilator drugs on venous tone in conscious rats

The dose-response effects of vasodilator drugs, nitroglycerin, sodium nitroprusside and hydralazine, on mean arterial pressure (MAP) and mean circulatory filling pressure (MCFP), an index of body venous tone, were investigated in conscious, unrestrained, intact rats as well as in rats treated with the ganglionic blocker, hexamethonium. The effects of these drugs were compared with those of the vehicle, normal saline, in control rats. In intact rats, i.v. infusion of nitroglycerin did not alter MAP while i.v. infusions of nitroprusside or hydralazine caused dose-dependent decreases in MAP. After ganglionic blockade, all three drugs decreased MAP. In intact rats, nitroglycerin and sodium nitroprusside did not affect MCFP but hydralazine increased MCFP. After treatment with hexamethonium, all three drugs decreased MCFP. The decreases in MCFP caused by nitroglycerin and nitroprusside, but not that by hydralazine, were significantly greater than the corresponding changes in control rats. Thus, in intact rats, the direct venodilator actions of nitroprusside and nitroglycerin were masked by endogenous sympathetic tone. When sympathetic nerve activity was attenuated, both nitroprusside and nitroglycerin have venodilator effects. Hydralazine, on the other hand, had insignificant venodilator effect both in the presence and absence of sympathetic reflexes.

Are agiotensin receptors in vascular smooth muscles a homogeneous population

The effects of angiotensin II (AII) and angiotensin III (AIII) on mean arterial pressure (MAP) and mean circulatory filling pressure (MCFP), an index of total body venous tone, in the presence and absence of [Sar1,Ile8]AII in conscious rats were examined. The infusion of AII caused dose-dependent increases in MAP and MCFP. The dose-response curves of MAP and MCFP for AII were displaced to the right in the presence of various doses of [Sar1,Ile8]AII. The pA2 values obtained for AII in the presence of the antagonist were 9.2 and 8.4 for the arterioles and veins respectively. The infusion of AIII also caused dose-dependent increases in MAP and MCFP. In the presence of the antagonist the AIII dose-response curves for MAP and MCFP were not displaced to right. The same maximum MAP was obtained for both AII and AIII but the maximum MCFP obtained following the infusion of AIII was smaller than that for AII. It is concluded that AII may act on different sub-classes of angiotensin receptors in arterioles and veins. AIII caused vasoconstriction in arterioles by acting on a sub-class of angiotensin receptors different from the ones activated by AII. AIII may act as a partial agonist on the same types of receptors as AIII in the venous bed.

Influence of intravenous infusion of ethanol on regional blood flow in conscious rats

Abstract— The effects of intravenous infusions of ethanol and saline (0·9% NaCl) on mean arterial pressure (MAP), heart rate (HR), total peripheral resistance (TPR), cardiac contractility (dP/dtmax) and systemic haemodynamics were studied in conscious, unrestrained rats by the radioactive microsphere technique. Saline (0·03 and 0·06 mL min−1 kg−1 for 12 min each dose) in the time‐control group did not affect MAP, HR, TPR, dP/dtmax or vascular conductances in any organs or beds. While the low dose ethanol (2·4 mg min−1 kg−1) did not alter MAP, HR, TPR, systemic haemodynamics or dP/dtmax, the high dose (4·8 mg min−1 kg−1) slightly reduced MAP and TPR but did not affect HR, cardiac output or dP/dtmax. Both doses of ethanol vasodilated the intestine and spleen, but vasoconstricted the skin. The high dose caused additional vasodilatation in the heart and testes and the low dose also constricted the skeletal muscle bed. Our results show that ethanol, at non‐hypotensive or slightly hypotensive doses, has marked vasodilator effects in the heart, intestine, spleen and testes.

Vasodilatation produced by adenosine in isolated rat perfused mesenteric artery: a role for endothelium

Adenosine and adenosine triphosphate (ATP) induced vasodilatation was studied in isolated rat perfused mesenteric artery at constant flow. Decrease in perfusion pressure was measured after induction of tone by continuous infusion with phenylephrine (5–7 μM). Adenosine and ATP caused dose-dependent vasodilatation. Following infusion with selective A2 adenosine receptor antagonist, 3,7-dimethyl-l-propargylxanthine (DMPX) (10 μM), or non-selective adenosine receptor antagonist, theophylline (30 μM), vasodilatation produced by adenosine were significantly reduced at lower doses. Responses to adenosine were not affected by pretreatment of tissues with either the P2-purinoceptor desensitizing agent, α, β methylene ATP (30 μM), or the P2-purinoceptor antagonist, suramin (10 μM). In contrast, both α, β methylene ATP and suramin significantly attenuate relaxation produced by ATP. Further, it was found that relaxation elicited by either adenosine or ATP was not significantly affected by the presence of glibenclamide (30 μM). Vasodilatation induced by adenosine and ATP was greatly reduced in denuded arteries but more so for ATP than adenosine. It is concluded that adenosine-mediated vasodilatation may hardly be due to the stimulation of A2 adenosine receptors and is strongly dependent on the presence of functional endothelium whereas ATP-mediated vasodilator responses were mediated via the activation of P2y-purinoceptors and appeared to be entirely dependent upon the presence of functional endothelium. Further, vasodilator responses to neither adenosine nor ATP were sensitive to inhibition by the potassium channel blocker glibenclamide, in isolated mesenteric perfused bed. This would imply that ATP-sensitive potassium channels were not involved in adenosine and ATP mediated vasodilatation.

Direct and indirect effects of angiotensin II on venous tone in conscious rats

The direct and indirect effects of angiotensin II (ANGII) on mean arterial pressure (MAP) and mean circulatory filling pressure (MCFP), an index of body venous tone, were investigated in conscious rats. Dose-response curves of ANGII were constructed in control rats (Group I), rats pretreated with saralasin (competitive ANGII antagonist, Group II), with guanethidine (inhibitor of sympathetic postganglionic neurons. Group III), or the ganglionic blocker hexamethonium (Group IV) and rats given unilateral right adrenalectomy two days prior to the study (Group V). The infusion of single doses of ANGII in control, adrenalectomized, guanethidine-treated and hexamethonium-treated rats dose dependently increased MAP to similar maxima; ED50 value was increased by adrenalectomy but unaffected by guanethidine nor hexamethonium. The pressor effects of ANGII was almost completely abolished by saralasin. ANGII dose dependently increased MCFP in control rats. In hexamethonium-treated rats, ANGII also dose relatedly increased MCFP which reached similar maximum as that in control rats, but the ED50 value was reduced. Saralasin almost completely abolished the MCFP response. Both guanethidine and adrenalectomy reduced maximum MCFP response to ANGII, but neither altered the ED50 value. Our results show that the sympathetic nervous system contributed greater to the MCFP than MAP effects of ANGII. Both direct and indirect effects of ANGII are mediated via the activation of ANGII receptors that are susceptible to blockade by saralasin.

[Sar1Ile7]angiotensin III, a new selective antagonist of the pressor effect of angiotensin III in conscious rats

Two analogues of angiotensin III were compared as antagonists of the pressor response to angiotensin II (ANG II) and angiotensin III (ANG III) in conscious, unrestrained rats. Dose-mean arterial pressure (MAP) response curves were obtained for ANG II and ANG III in the absence or presence of [Ile7]ANG III (1.3 x 10(-7) mol/kg) or [Sar1 Ile7]ANG III (1.2 x 10(-7) mol/kg). In the presence of [Ile7]ANG III, the dose-MAP response curves for ANG II and ANG III were significantly displaced to the right. [Ile7]ANG III behaved as a partial agonist on ANG II but not ANG III receptors. In the presence of [Sar1 Ile7]ANG III, the dose-MAP response curve for ANG III but not ANG II was significantly displaced to the right. This suggests that [Sar1 Ile7]ANG III is a selective antagonist of ANG III in the vasculature. [Ile7]ANG III, on the other hand, antagonizes both ANG II and ANG III receptors. Our results support the hypothesis of the existence of a sub-class of angiotensin receptors activated by ANG III in the vascular smooth muscle.

EFFECTS OF CALCIUM CHANNEL ANTAGONISTS AND PERTUSSIS TOXIN ON NORADRENALINE-INDUCED CONTRACTIONS IN PULMONARY ARTERY FROM PULMONARY HYPERTENSIVE RATS

The influence of calcium channel antagonists, felodipine and cadmium, as well as pertussis toxin on noradrenaline-induced contractions in pulmonary artery rings from rats with pulmonary hypertension induced by monocrotaline (MCT) were examined. MCT-treated rats had pulmonary hypertension, right ventricular hypertrophy and lung oedema, as compared to corresponding vehicle-treated rats. The MCT-treated animals did not have polycythemia as compared to vehicle-treated rats. Pre-treatment of pulmonary artery rings from MCT-treated rats with felodipine and cadmium significantly reduced the maximum response without altering the EC50 or the Hill coefficient of concentration-response curve to noradrenaline. In pulmonary artery rings from vehicle-treated rats, felodipine significantly increased the EC50 and reduced the maximum response and the Hill coefficient of the concentration-response curve to noradrenaline. In contrast, cadmium did not alter these parameters in pulmonary artery rings from vehicle-treated rats. Pertussis toxin did not affect noradrenaline-induced contractions in pulmonary artery rings from vehicle- or MCT-treated rats. Felodipine, cadmium and pertussis toxin were ineffective in inhibiting noradrenaline-induced contractions in aortic rings from either vehicle- or MCT-treated rats. Our results can be interpreted to indicate that alteration to voltage operated, felodipine-sensitive, calcium channels as well as, cadmium-sensitive sites contribute to the changes observed in the functional behavior of pulmonary blood vessels from pulmonary hypertensive rats.

Pressor Response to β1- and β2-Blockers in Conscious Rats Treated with Phentolamine

The purpose of this study was to examine the conditions whereby β-blockers cause a pressor response in conscious, unrestrained rats: (1) whether β-blockers cause a pressor response in rats subjected t