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

Cai, Guoping; Gürdal, Hakan; Seasholtz, Tammy M.; Johnson, Mark D.

doi:10.1016/0047-6374(94)91587-3

Cited by 11 publications

(6 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A marked reduction of Ang II-induced contraction in only 40-week SHR aortic rings with blocking of the AT2R-related signaling pathways (Figure 2) provided further information that reduced AT1R-contraction in aged SHR would result from any reduction of AT1R-related signaling cascade by hypertension regardless of enhanced AT1R expression with age. A similar spectrum was also obtained in aged Fisher 344 rats [22] and in SHR [23]. Alternatively, as Arun et al reported [24], altered [Ca 2+ ] i incorporation through reduction in the AT1R-coupled VDCC phosphorylation pathway may be involved in the reduced contraction by Ang II in aged SHR.…”

Section: Discussionsupporting

confidence: 75%

Attenuation of L-Type Ca2+ Channel Expression and Vasomotor Response in the Aorta with Age in Both Wistar-Kyoto and Spontaneously Hypertensive Rats

et al. 2014

View full text Add to dashboard Cite

Age-related vascular diseases are induced by vascular dysfunction, which involves changes in the vasomotor response. The voltage-dependent L-type calcium channel (VDCC) protein is involved in the regulation of vessel function (contraction/relaxation action). In the present study, we evaluated age-related vasomotor function and expression of the signal-related target proteins, including VDCC, using thoracic aorta from both 8- and 40-week old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). In contraction experiments using aortic rings, vasomotor responses of both phenylephrine-induced contraction and acetylcholine-induced relaxation were significantly attenuated with age in SHR, whereas WKY did not lose activity with age. Contraction induced by angiotensin II was impaired only for the 40-week old SHR among all the rat groups tested, although enhanced AT1R/reduced AT2R expression with age was observed for both WKY and SHR. In contrast, a vasomotor responsiveness to Bay K 8644 (a VDCC agonist) at the initial contraction phase was significantly attenuated in both 40-week WKY and SHR with significant reduction of VDCC protein expression. The reduced VDCC expression in 40-week old rats significantly lowered the relaxation activity of VDCC blockers, such as verapamil and Trp-His, but did not affect that of nifedipine. Taken together, we provided the first evidence that aging caused a reduction of VDCC expression in rat aorta, irrespective of the rat strain, along with diminishment of the therapeutic potential of VDCC blockers.

show abstract

Section: Discussionsupporting

confidence: 75%

Attenuation of L-Type Ca2+ Channel Expression and Vasomotor Response in the Aorta with Age in Both Wistar-Kyoto and Spontaneously Hypertensive Rats

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Information regarding the potential effects of age and sex on angiotensin receptors in human subjects or animal models is sparse. 20,21 Our data suggest a complex interaction between age, sex, heart failure, and cardiac Ang II receptor concentration.…”

Section: Discussionmentioning

confidence: 98%

Differential Regulation of Cardiac Angiotensin Converting Enzyme Binding Sites and AT ₁ Receptor Density in the Failing Human Heart

et al. 1998

View full text Add to dashboard Cite

show abstract

“…To explore the hypothesis that receptor gain is physiologically regulated, the present experiments examined differences in gain associated with maturation and responses to acute hypoxia, both previously shown to alter receptor-IP 3 coupling (7,9,49). In studies from our own laboratory, we have demonstrated that both age and acute hypoxia can modulate receptor density and agonist affinity, at least for serotonin in ovine carotid arteries (4).…”

Section: R414mentioning

confidence: 99%

“…Each of these factors appears to be under physiological control for many different receptor types. For example, both receptor density and agonist affinity for a given receptor type can vary dramatically with age (12), tissue (7), or environmental conditions such as chronic hypoxia (15). In addition, members of the recently discovered family of regulators of G protein-signaling (RGS) proteins also appear to function as modulators of the coupling between receptor binding and intracellular effector activation (20).…”

mentioning

confidence: 99%

Effects of maturation and acute hypoxia on receptor-IP₃coupling in ovine common carotid arteries

Angeles

Williams

Purdy

et al. 2001

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Whereas previous studies have established that many mechanisms mediating pharmacomechanical coupling are subject to regulation, evidence of physiological regulation of the coupling efficiency between receptor activation and second-messenger production is scarce. The present studies address the hypothesis that acute hypoxia and maturation can influence the mass of second-messenger production for each activated agonist-bound receptor ("receptor gain"). For this assessment, receptor density and agonist affinity values were used to calculate 5-hydroxytryptamine (5-HT) concentrations that would produce standardized numbers of bound receptors (8.5 fmol/mg protein) in each experimental group and thus minimize effects of age or hypoxia on receptor density or agonist affinity. After 3 min of exposure to these 5-HT concentrations, normoxic magnitudes of contraction were similar (as %potassium maxima) in fetal (50 +/- 14%) and adult (40 +/- 9%) arteries, but hypoxia (PO(2) approximately 9--12 Torr for 30 min) depressed contractile tensions with a significantly different time course and magnitude in fetal (30 +/- 10%) and adult (17 +/- 11%) arteries (P < 0.05). Basal inositol 1,4,5-trisphosphate (IP(3)) values (in pmol/mg protein) were significantly greater in fetal (94 +/- 16) than in adult (44 +/- 6) arteries, and integrated areas above baseline for the IP(3) time courses (in nmol-s/mg protein) were significantly greater in fetal than in adult arteries both in normoxic (14.3 +/- 1.8 vs. 9.1 +/- 1.6) and hypoxic (15.0 +/- 2.1 vs. 8.6 +/- 1.2) conditions (P < 0.05). Hypoxia altered the IP(3) time courses both in the fetus and the adult but had no significant effect on IP(3 )mobilization or receptor gain. These data demonstrate that for the 5-HT(2a) receptor predominant in this preparation, receptor gain can be experimentally determined, is not influenced by acute hypoxia, but is greater in fetal than in adult ovine carotid arteries.

show abstract

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

Cited by 11 publications

References 22 publications

Attenuation of L-Type Ca2+ Channel Expression and Vasomotor Response in the Aorta with Age in Both Wistar-Kyoto and Spontaneously Hypertensive Rats

Attenuation of L-Type Ca2+ Channel Expression and Vasomotor Response in the Aorta with Age in Both Wistar-Kyoto and Spontaneously Hypertensive Rats

Differential Regulation of Cardiac Angiotensin Converting Enzyme Binding Sites and AT ₁ Receptor Density in the Failing Human Heart

Effects of maturation and acute hypoxia on receptor-IP₃coupling in ovine common carotid arteries

Contact Info

Product

Resources

About

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

Cited by 11 publications

References 22 publications

Attenuation of L-Type Ca2+ Channel Expression and Vasomotor Response in the Aorta with Age in Both Wistar-Kyoto and Spontaneously Hypertensive Rats

Attenuation of L-Type Ca2+ Channel Expression and Vasomotor Response in the Aorta with Age in Both Wistar-Kyoto and Spontaneously Hypertensive Rats

Differential Regulation of Cardiac Angiotensin Converting Enzyme Binding Sites and AT 1 Receptor Density in the Failing Human Heart

Effects of maturation and acute hypoxia on receptor-IP3coupling in ovine common carotid arteries

Contact Info

Product

Resources

About

Differential Regulation of Cardiac Angiotensin Converting Enzyme Binding Sites and AT ₁ Receptor Density in the Failing Human Heart

Effects of maturation and acute hypoxia on receptor-IP₃coupling in ovine common carotid arteries