Effects of α‐adrenoceptor agonists on cardiac output and its regional distribution in the pithed rat

Abstract

ICardiac output, its distribution and tissue blood flows were determined with tracer microspheres in pithed rats during pressor responses elicited by either x,-adrenoceptor agonists (tirazoline, phenylephrine) or a2-adrenoceptor agonists (xylaxine, B-HT 933). Two doses were used for each of cirazoline and B-HT 933 and phenylephrine was investigated in the presence of propranolol (3 mg kg-'). The rats were pithed under halothane anaesthesia. 2 Cardiac output was increased by xylazine, the higher dose of B-HT 933 and phenylephrine. Heart rate was increased by phenylephrine and the higher doses of both cirazoline and B-HT 933. Stroke volume was greater in those groups given xylazine, phenylephrine and the higher dose of B-HT 933 but was decreased in those animals given the higher dose of cirazoline. 3 Both M2-adrenoceptor agonists increased the number of microspheres trapped in the lungs and the proportion ofthe cardiac output passing through the hepatic artery but decreased that flowing through the spleen and gastrointestinal tract. The higher dose of B-HT 933 also decreased the fraction of cardiac output fiowing to the kidneys but kidney blood flow was maintained as a result of the increased cardiac output. Also, this treatment reduced blood flow in the epididimal fat pads. 4 Both a,-adrenoceptor agonists increased the fraction of cardiac output received by the coronary vasculature but the only other effect on distribution common to these agents was an increase in the percentage of the cardiac output passing to the hepatic artery. Cirazoline decreased the proportion of cardiac output distributed to the gastrointestinal tract and spleen but the total fraction of cardiac output passing to the hepatosplanchnic region was maintained as a result of the increase to the hepatic artery.5 Cirazoline markedly reduced the proportion of the cardiac output received by the kidneys and absolute flow in these organs was only 1.4% of control after the higher dose of this agonist but flow at the lower dose was maintained by the higher cardiac output. 6 It is concluded that there is a significant contribution to the pressor responses elicited by x-agonists resulting from an oc-adrenoceptor-mediated increase in cardiac output that may result from greater heart rates or stroke volumes. Also, there is a differential distribution of cx-receptor subtypes throughout the vasculature which is especially noticeable in the kidneys.

Effect of artificial respiratory volume on the cardiovascular responses to an α1‐ and an α2‐adrenoceptor agonist in the air‐ventilated pithed rat

“…The effects of phenylephrine and xylazine (at the control respiratory volume of 20 ml kg -) on cardiac output, regional distribution of cardiac output and regional blood flow were essentially the same as previously reported and discussed (Hiley & Thomas, 1987). One notable feature is, however, that phenylephrine increased heart rate at respiratory volumes of 15 and 30mlkg-1.…”

“…This is not likely to be due to f-adrenoceptor stimulation because of the presence of propranolol at a dose sufficient to abolish the heart rate response to 50ng isoprenaline (C.R. Hiley, unpublished observations) and it has previously been shown that this heart rate response to phenylephrine is removed by the administration of prazosin (Hiley & Thomas, 1987). Also ar-adrenoceptors mediating tachycardia have been reported by Flavahan & McGrath (1981) and 89% for 15 and 30mlkg-1 respectively), whilst that to the hepatosplanchnic bed as a whole was greatest at the lowest respiratory volume (39% as compared with 17% and 155% for 20 and 30 ml kg-' respectively).…”

“…They also found that hypoxia combined with hypercapnia selectively depressed the pressor responses to phenylephrine although these responses were enhanced as Pao2 increased. This suggested that differences in blood gases (Kalkman et al, 1984;Hiley & Thomas, 1987). Also, selective a-adrenoceptor agonists differentially affect the regional distribution of cardiac output and organ blood flow (Hicks & Waldron, 1983;Waldron & Hicks, 1985;Hiley & Thomas, 1987 Newbury, Berkshire) was given as a 0.5 mg bolus followed by a 100 pg min1l infusion.…”

Pressor effects of the α2‐adrenoceptor agonist B‐HT 933 in anaesthetized and haemorrhagic rats: comparison with the haemodynamic effects of amidephrine

“…Previously we have observed that, in anaesthetized rats, following an initial depressor i.v. dose of the a2-adrenoceptor agonist, B-HT 933, subsequent administration of B-HT 933 induced dose-dependent pressor responses (MacLean et al, 1988) similar in haemodynamic profile to those described in the pithed rat by Hiley & Thomas (1987). aAdrenoceptor agonists induce systemic pressor responses in pithed rats by increasing both cardiac output and total peripheral resistance (Kalkman et al, 1984;Hiley & Thomas, 1987;MacLean & Hiley, 1988a,b).…”

“…aAdrenoceptor agonists induce systemic pressor responses in pithed rats by increasing both cardiac output and total peripheral resistance (Kalkman et al, 1984;Hiley & Thomas, 1987;MacLean & Hiley, 1988a,b). The a1-adrenoceptor agonist phenylephrine and the a2-adrenoceptor agonists B-HT 933 and xylazine induce these pressor responses without reducing blood flow through the renal vascular bed, indeed phenylephrine was seen to increase renal blood flow (Hiley & Thomas, 1987).…”