Guoping Cai

α1-Adrenoceptor responsiveness in the aging aorta

Abstract Previous studies from this laboratory have shown that aortic α 1 -adrenoceptor-mediated responsiveness is altered during maturation and aging. This study examines the possibility that there is a change in the α 1 -adrenoceptor subtypes in the aorta during maturation and aging. The apparent affinity of norepinephrine, as determined by partial receptor inactivation with the α 1 -adrenoceptor antagonist phenoxybenzamine, was found to be higher in 1-month-old rats compared to 6- and 24-month-old rats. The α 1B -adrenoceptor subtype-selective antagonist chlorethylclonidine was used to examine possible heterogeneity in aortic α 1 -adrenoceptors. The inhibitory effect of chlorethylclonidine on norepinephrine-stimulated contraction was greater in young animals compared to aged animals. Chlorethylclonidine blocked norepinephrine-stimulated inositol phosphate accumulation in 1-month-old aorta but it produced only partial inhibition in the 6- and 24-month-old aortas. The relatively non-selective α 1 -adrenoceptor antagonists phenoxybenzamine (0.1 μM) and prazosin (0.1 μM) inhibited inositol phosphate accumulation and contractile responses in all ages. The complete block of α 1 -adrenoceptor-mediated responses by chlorethylclonidine in younger animals shows that α 1 -adrenoceptor-mediated responses are mediated by the chlorethylclonidine-sensitive α 1 -adrenoceptor subtypes. The partial inhibition by chlorethylclonidine of α 1 -adrenoceptor-mediated responses in 6- and 24-month-old animals indicates an increased role of an α 1 -adrenoceptor subtype that is relatively insensitive to chlorethylclonidine.

Cardiovascular hypertrophy and increased vascular contractile responsiveness following repeated cocaine administration in rabbits

The effects of repeated cocaine administration on contractile responses were studied in adult rabbits. Repeated cocaine exposure caused a significant increase in the maximal response of the aorta to the agonists norepinephrine and serotonin as well as the receptor- independent stimulus KCl when compared to the saline controls. Cocaine exposure caused a significant increase in the wet weights of both heart and aorta. When the contraction was normalized to the wet weight of the aorta there was no difference between rabbits administered cocaine and saline. Acute cocaine administration caused a time-dependent increase in immunoreactivity of the proto-oncogene c-Fos in the aorta. These results show that repeated cocaine administration leads to the development of cardiovascular hypertrophy.

Age-related changes in angiotensin II-stimulated vascular contraction and inositol phosphate accumulation in Fischer 344 rats

This study examined the influence of age on angiotensin II (AII)-stimulated vascular contractile responses and inositol phosphate (IP) accumulation in Fischer 344 rats. In the aorta, AII-stimulated contraction and IP accumulation were markedly reduced in 6- and 24-month-old rats compared to 1-month-old rats. There was not a significant difference in the contractile response to AII between 6- and 24-month-old rats, although IP hydrolysis showed a further decrease between 6 and 24 months. In tail artery, there were no differences in contraction and phosphoinositol metabolism in response to AII in the different ages. Losartan blocked AII-stimulated vascular contraction and IP hydrolysis in both aorta and tail artery while PD123319 did not inhibit either response. These data indicate that during maturation, there is a decline in AII-stimulated aortic contraction and IP accumulation in aorta but not in tail artery and these changes are due to altered AT1 receptor function.

Prenatal cocaine exposure affects the development of aortic adrenergic innervation and contractile responses

This study examines the effects of prenatal cocaine administration on the development of vascular sympathetic innervation and contractile responsiveness. Rabbits received cocaine (4 mg/kg, iv, bid) or saline during gestational days 8 to 29. Aortas were obtained on postnatal days 10, 20, 30 and 50. Vascular smooth muscle responsiveness was assessed by measuring aortic contractile responses to norepinephrine (NE) and to other vasoconstrictors. Vascular adrenergic innervation was evaluated by measuring desipramine sensitive [3H]-NE uptake into aortic ring segments and aortic NE content. [3H]-NE uptake and NE content were reduced at postnatal days 10 and 20 in the rabbits exposed prenatally to cocaine. Differences were not observed at postnatal days 30 or 50. The contractile response to NE was reduced in rabbits exposed to cocaine prenatally. Maximal response and potency were decreased at postnatal day 10 and potency was still decreased at day 20, but not at the older ages. Contractile responses to serotonin (5-HT) and angiotensin II (AII) were not affected by prenatal cocaine exposure. These results suggest that prenatal cocaine exposure delays the development of aortic adrenergic innervation and alpha adrenoceptor responsiveness.