Contractile responses of rat aorta to phenylephrine and serotonin, and aging

Takayanagi, Issei; Onozuka, Shuji; Ohtsuki, Hiroshi; Shinkai, Michiko

doi:10.1016/0306-3623(91)90312-t

Cited by 7 publications

(5 citation statements)

References 22 publications

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“…In contrast to previous studies in the ma turing rat [12,13,17,18] an increase in the sensitivity (EC50 value) and /or maximal con traction to virtually all receptor-and non receptor-mediated agents were observed in both aorta and tail artery from 3 week-old rats when compared to 7-and 11-week-old ani mals. The only exception was a decrease in the maximal response with no change in the sensitivity of aorta from 3-week-old rats to 5-HT.…”

Section: Discussioncontrasting

confidence: 52%

Ontogeny of Vascular Smooth Muscle Responsiveness in the Postweaning Rat

Soltis

Newman²

1992

Dev Pharmacol Ther

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This study investigated the ontogeny of contractile and relaxation responses in aortic and tail artery preparations from 3-, 7-, and 11-week-old male Sprague-Dawley rats. Contractile responses to norepinephrine, serotonin, KCl, electrical stimulation, and potassium-free physiological solution were significantly increased in vascular smooth muscle from 3-week-old rats when compared to 7- and 11-week-old rats. Endotheliumdependent acetylcholine-induced relaxation and β-adrenoceptor mediated isoproterenol-induced relaxation were significantly attenuated with maturation. These data demonstrate that significant changes occur in aortic and tail artery smooth muscle responsiveness during the postweaning maturational period of the rat. The alterations may have significant implications with regard to cardiovascular and thermoregulatory function as well as the age of the animal when utilized as an experimental model for identifying pathogenic mechanisms involved in various disease states such as hypertension. As such, further studies are warranted to determine if similar ontogenie changes in vascular function occur at the level of the resistance vessel.

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Section: Discussioncontrasting

confidence: 52%

Ontogeny of Vascular Smooth Muscle Responsiveness in the Postweaning Rat

Soltis

Newman²

1992

Dev Pharmacol Ther

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“…While a few reports have assessed age-dependent effects on a,-adrenergic-and 5hydroxytryptamine, (5-HT2)-receptor reserves in isolated vasculature O'Donnell, 1988, 1989;Takayanagi and Yamasawa, 1989;Takayanagi et al, 1991;Takayanagi and Koike, 19911, none of these reports has provided an explicit measure of agonist efficacy, such as 7, and moreover, there is a relative paucity of information concerning the effects of the diabetic state on agonist efficacy. In this regard, the results of this study are consistent with previous reports that have documented an apparent subsensitivity of diabetic rat aorta to contractile responses elicited by single agonist activation of the a,-adrenergic [Turlapaty et al, 1980;Pfaffman et al, 1982;Ramanadham et al, 1984;Head et al, 19871 and 5-HT2 [MacLeod and McNeill, 1981;Head et al, 19871 receptors.…”

Section: Discussionmentioning

confidence: 99%

“…The goal of these studies was two-fold: first, to use the operational efficacy parameter, T, to attempt to shed more mechanistic insight on previously reported age- O'Donnell, 1988, 1989;Takayanagi et al, 1989Takayanagi et al, , 1991Takayanagi and Koike, 19911 and diabetes-related [Turlapaty et al, 1980;Pfaffman et al, 1982;Ramanadham et al, 1984;Head et al, 1987;McNeill, 1981, 1982, 19851 alterations in rat aortic reactivity in response to activation of the a,-adrenergic and 5-hydroxytryptamine, (5-HT,) receptor subtypes; second, to compare the efficacy estimates (T) so obtained with the more traditional model-independent efficacy estimates described above. To this end, steady-state contractile responses elicited by PE (pheny1ephrine)-and 5-HT activation of the a,-adrenergic and 5-HT2 receptor subtypes, respectively, were examined in isolated aortic rings derived from agematched control, streptozotocin (STZ)-diabetic (of 8 weeks duration), and senescent (24month-old) male Fischer 344 (F-344) rats.…”

Section: Introductionmentioning

confidence: 99%

Age‐ and pathology‐dependent alterations in the efficacy of phenylephrine‐ and 5‐hydroxytryptamine‐induced contractions in isolated rat aorta

Christ

1992

Drug Development Research

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Christ, G.J.: Age-and pathology-dependent alterations in the efficacy of phenylephrineand 5-hydroxytryptamine-induced contractions in isolated rat aorta. Drug Dev. Res. 25: 303-31 4, 1992. Male Fischer 344 rats were made diabetic for 8-9 weeks by a single intraperitoneal injection of streptozotocin. Steady-state contractile responses elicited by 5-hydroxytryptamine (5-HT) and phenylephrine (PE) activation of the 5-HT2-and a,-adrenergic receptors, respectively, were studied in aortic rings from diabetic, age-matched control and 24-month-old (senescent) F-344 rats. Concentration-response curves (CRCs) for PE and 5-HT were analyzed by the Black and Leff operational model of pharmacological agonism to determine efficacy (T) and slope factor values. Efficacy estimates obtained with the operational model were compared to two commonly used model-independent estimates of agonist efficacy; 1) Stephenson's efficacy estimate (e), and 2) the estimation of agonist receptor reserves. The estimated T for PE in aortic rings from age-matched control animals (12.38) was significantly reduced by both experimental diabetes (4.52) and senescence (7.1 2), and these findings were in agreement with results obtained using the model-independent efficacy estimates. However, with respect to 5-HT-induced contractions, the estimated T in age-matched control animals (2.46) was also significantly reduced by both diabetes (1 58) and senescence (1.69), but these alterations were not detected by the model-independent efficacy esti- 304Christ mates. In all cases, a decrease in operational efficacy, T , was associated with a decrease in the asymptote of the PE or 5-HT CRC (expressed as the agonist maximal effect (Emax)/ tissue maximal effect (Tma) and/or alterations in the fractional occupancy/response relationship. In addition, T was sensitive to small changes in agonist efficacy that occurred in the absence of any apparent alterations in the occupancy/response relationship. As such, these studies extend our previous observations in rat aorta to highlight the advantages of using the Black and Leff efficacy estimate, T , rather than other commonly used model-independent estimates of agonist efficacy. o 1992 Wiley-Liss, Inc.

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“…Whether alpha adrenergic responsiveness alters with aging is less clear. In vitro animal studies have shown both an increased[I], reduced [2,3] or unchanged [4] al-mediated phenylephrine response. In vitro human studies have shown an increased [5] or reduced [6] ~l-mediated phenylephrine response in isolated artery preparations.…”

Section: Introductionmentioning

confidence: 99%