Cardiac actions of central but not peripheral urotensin II are prevented by beta-adrenoceptor blockade.
Urotensin II (UII) is a highly conserved peptide that has potent cardiovascular actions following central and systemic administration. To determine whether the cardiovascular actions of UII are mediated via beta-adrenoceptors, we examined the effect of intravenous (IV) propranolol on the responses to intracerebroventricular (ICV) and IV administration of UII in conscious sheep. Sheep were surgically instrumented with ICV guide tubes and flow probes or cardiac sympathetic nerve recording electrodes. ICV UII (0.2 nmol/kg over 1 h) caused prolonged increases in heart rate (HR; 33 +/- 11 beats/min; P < 0.01), dF/dt (581 +/- 83 L/min/s; P < 0.001) and cardiac output (2.3 +/- 0.4 L/min; P < 0.001), accompanied by increases in coronary (19.8 +/- 5.4 mL/min; P < 0.01), mesenteric (211 +/- 50 mL/min; P < 0.05) and iliac (162 +/- 31 mL/min; P < 0.001) blood flows and plasma glucose (7.0 +/- 2.6 mmol/L; P < 0.05). Propranolol (30 mg bolus followed by 0.5 mg/kg/h IV) prevented the cardiac responses to ICV UII and inhibited the mesenteric vasodilatation. At 2 h after ICV UII, when HR and mean arterial pressure (MAP) were increased, cardiac sympathetic nerve activity (CSNA) was unchanged and the relation between CSNA and diastolic pressure was shifted to the right (P < 0.05). The hyperglycemia following ICV UII was abolished by ganglion blockade but not propranolol. IV UII (20 nmol/kg) caused a transient increase in HR and fall in stroke volume; these effects were not blocked by propranolol. These results demonstrate that the cardiac actions of central UII depend on beta-adrenoreceptor stimulation, secondary to increased CSNA and epinephrine release, whereas the cardiac actions of systemic UII are not mediated by beta-adrenoreceptors and probably depend on a direct action of UII on the heart.
Hood
S G
SG
Howard Florey Institute, University of Melbourne, Parkville, Vic. 3010, Australia.
Watson
A M D
AM
May
C N
CN
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012756:Sheep; D013564:Sympathetic Nervous System / Q000187:drug effects; D014579:Urotensins / Q000008:administration & dosage* / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D014579:Urotensins; C029677:urotensin II; D011433:Propranolol