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Cardiovascular hyporesponsiveness to norepinephrine, propranolol and nitroglycerin in portal‐hypertensive and aged rats
Author(s) -
Polio John,
Sieber Cornel C.,
Lerne Emanuel,
Groszmann Roberto J.
Publication year - 1993
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840180120
Subject(s) - propranolol , medicine , norepinephrine , portal hypertension , endocrinology , blood pressure , vascular resistance , hemodynamics , splanchnic , portal venous pressure , heart rate , adrenergic , sympathetic nervous system , mean arterial pressure , cirrhosis , dopamine , receptor
Most studies testing vasoactive agents in portalhypertensive rats have been performed in young animals. To assess age‐related changes in hemodynamic responses to adrenergic stimuli, we examined (a) responsiveness to norepinephrine (0.14 to 12.0 μg ˙ kg −1 ˙ min −1 ) in young (3‐mo‐old) and aged (9‐mo‐old) sham‐operated and portal‐hypertensive rats and (b) response to propranolol (2 and 10 mg ˙ kg −1 body wt), nitroglycerin (3.6 mg ˙ kg −1 ˙ min −1 ) or saline solution in aged portal‐hypertensive rats. Aged rats exhibited significantly (p < 0.05) smaller responses to norepinephrine with regard to increases in mean arterial pressure and superior mesenteric arterial vascular resistance, irrespective of portal hypertension. Portal hypertension alone potentiated this reduced response in aged animals and was associated with cardiovascular hyporesponsiveness to norepinephrine in young rats. Portal pressure was significantly (p < 0.05) lower in aged sham‐operated rats than in young sham‐operated rats over a wide range of norepinephrine doses. Portal‐hypertensive aged rats showed significantly (p < 0.05) lower heart rates. Furthermore, systemic and splanchnic cardiovascular responses to propranolol and nitroglycerin mediated by the sympathetic nervous system were decreased or negligible in aged rats, compromising the portal‐hypotensive effects of these drugs. In summary, aged rats express diminished cardiovascular responsiveness to adrenergic stimuli. Therefore age should be considered an important factor in studies evaluating pharmacological agents for the treatment of portal hypertension. (H EPATOLOGY 1993;18:128–136).