Effect of chronic exposure to cold on isoprenaline-induced cAMP accumulation and relaxation in the rat aorta
Introduction
Rats chronically exposed to cold temperature develop hypertension, tachycardia and cardiac hypertrophy (Fregly et al., 1989, Papanek et al., 1991). These rats showed greater metabolic, cardiac and vascular responsiveness to noradrenaline and β-adrenergic agonists. For example, Wickler et al. (1984) have shown that isoprenaline, a β-adrenergic agonist, greatly increased blood flow to brown fat, cardiac and skeletal muscles in cold-adapted rats. Fregly et al. (1977) reported that isoprenaline-induced increase in tail skin and colonic temperature was greater in cold-adapted rats compared with rats maintained at room temperature. Similar observations have been made by other workers (Evonuk and Hannon, 1963, Depocas, 1960, Himms-Hagen, 1969, Jansky et al., 1967). Increased responsiveness to β-adrenergic agonists has also been observed in other systems. Isoprenaline-induced increase in heart rate is significantly greater in cold-acclimated rats (Barney et al., 1980, Fregly et al., 1977, Miller et al., 1979). In the vasculature, isoprenaline induced greater relaxation in arterial smooth muscles from cold-adapted rats (Bryar et al., 1983) compared with control rats maintained at room temperature. The fact that β-adrenoceptor blockade with propranolol enhanced the maximal contactile response to noradrenaline more in cold-acclimated rats (Bryar et al., 1983) would confirm greater β-adrenoceptor-mediated vascular smooth muscle relaxation in rats chronically exposed to cold temperature.
However, the mechanism responsible for the increased responsiveness to β-adrenoceptor activation was not addressed in any of the studies cited above (Fregly et al., 1977, Fregly et al., 1989, Wickler et al., 1984, Papanek et al., 1991, Evonuk and Hannon, 1963, Depocas, 1960, Himms-Hagen, 1969, Jansky et al., 1967, Bryar et al., 1983). Even though Bryar et al. (1983) suggested that cold acclimation could alter the biochemical events coupling receptor activation to response, no experimental data were provided to support this hypothesis. Stimulation of β-adrenoceptors on vascular smooth muscle results in relaxation, through activation of membrane-bound adenylyl cyclase. This results in an increase in cAMP with subsequent increase in activation of cAMP-dependent protein kinases (Anderson and Wilsson, 1977, Hardman, 1981, Krall et al., 1983). Increase in β-adrenoceptor activity could occur as a result of changes in pre-receptor (affinity and/or density) or post-receptor signaling mechanisms. Our main objective in this study was to compare isoprenaline-induced relaxation of isolated rat aorta from control and cold-acclimated rats and attempt to relate the differences to changes in receptor parameters (affinity and reserve) and signaling mechanisms.
Section snippets
Methods
Male Sprague–Dawley rats approximately 100 g were kept (1 rat per cage) in the cold room (5 °C) for a period of 5 weeks while age-matched littermates kept at room temperature (25 °C) served as controls. Rats in both groups were fed ad libitum and had access to water throughout the duration of the study. The study was approved by the Institutional research committee.
At the end of 5 weeks, each rat was anaesthetized with pentobarbital (sagatal, 50 mg/kg). Thereafter, one carotid artery was
Effect of cold exposure on arterial blood pressure
Chronically exposed rats to cold temperature (5 °C) for weeks developed hypertension. Arterial blood pressure was 119.4 ± 6.3 (n = 9) and 145.8 ± 11.5 (n = 6) in control and cold-treated rats, respectively. These values were significantly (p < 0.05) different from each other.
Effect of cold exposure on agonist-induced relaxations
Isoprenaline (10− 9–10− 5 M) produced reproducible concentration-dependent relaxation of the isolated rat aorta from control rats as well as rats chronically exposed to cold (Fig. 1). Tachyphylaxis was not observed in any of the
Discussion
Impaired β-adrenoceptor-mediated vascular smooth muscle relaxation is an established feature of hypertension. This has been demonstrated in humans (Brodde et al., 1987, Feldman, 1987, Michel et al., 1990) and various animal models (Feldman, 1987, Michel et al., 1990, Brodde and Michel, 1992) of hypertension. In deoxycorticosterone acetate (DOCA)-salt hypertensive rats and SHR, it has been shown that the facilitatory action of presynaptic β2-adrenoceptors was enhanced, while the number and
References (37)
Altered responsiveness of adenylate cyclase to adenosine and other agents in the myocardial sarcolemma and aorta of spontaneously-hypertensive rats
Biochemical Pharmacology
(1988)- et al.
Decreased beta-adrenoceptor-mediated vasodilation in aorta from aged rats: possible involvement of a stimulatory GTP-binding protein
European Journal of Pharmacology
(1991) - et al.
Alteration of prejunctional alpha 2-adrenergic autoinhibition in DOCA-salt hypertension
American Journal of Hypertension
(1995) - et al.
Role of cyclic nucleotides metabolism and mechanical activity in smooth muscle
- et al.
Evidence for reduced beta-adrenoceptor coupling to adenylate cyclase in femoral arteries from spontaneously hypertensive rats
British Journal of Pharmacology
(1988) - et al.
Role of stimulatory GTP-binding protein (Gs) in reduced beta-adrenoceptor coupling in the femoral artery of spontaneously hypertensive rats
British Journal of Pharmacology
(1988) - et al.
Reduced function of the stimulatory GTP-binding protein in beta adrenoceptor-adenylate cyclase system of femoral arteries isolated from spontaneously hypertensive rats
Journal of Pharmacology and Experimental Therapeutics
(1988) - et al.
Decreased responsiveness to beta-adrenoceptor agonists in arterial strips from spontaneously hypertensive rats is not associated with alterations in beta-adrenoceptors
Journal of Hypertension
(1991) - et al.
Changes in beta-adrenergic responsiveness of rats during chronic cold exposure
Journal of Applied Physiology
(1980) - et al.
Characteristics of hormone-stimulated adenylate cyclase in vascular smooth muscle: altered activity in spontaneously hypertensive rat
Blood Vessels
(1982)
Adrenergic receptors and their signal transduction mechanisms in hypertension
Journal of Hypertension
Alterations of β-adrenoceptor function in essential hypertension
Journal of Cardiovascular Pharmacology
Changes in vascular responsiveness following chronic exposure to cold in the rat
Journal of Applied Physiology
Changes in the vascular beta-adrenoceptor-activated signalling pathway in 2Kidney-1Clip hypertensive rats
British Journal of Pharmacology
Vascular relaxation in the spontaneously hypertensive rat
Journal of Cardiovascular Pharmacology
The calorigenic response of cold-acclimated white rats to infused noradrenaline
Canadian Journal of Biochemistry and Physiology
Cardiovascular function and norepinephrine-thermogenesis in cold-acclimated rats
American Journal of Physiology
Beta-adrenergic receptor alterations in hypertension—physiological and molecular correlates
Canadian Journal of Physiology and Pharmacology
Cited by (4)
The vasorelaxant effect of 8(17),12E,14-labdatrien-18-oic acid involves stimulation of adenylyl cyclase and cAMP/PKA pathway: Evidences by pharmacological and molecular docking studies
2015, European Journal of PharmacologyCitation Excerpt :Indeed, many reports show that KV channels are modulated by FSK or by PKA phosphorylation (Chai et al., 2005; Cole et al., 1996; Mason et al., 2002; Matthias et al., 2002; Waldron and Cole, 1999). The extracellular application of FSK or dibutyryl cAMP, a well-known cAMP analog, have been shown to prevented the contraction induced by norepinephrine in rat aorta (Lincoln and Fisher-Simpson, 1984) as well as to relax that tissue pre-contracted by PE (El-Hajj and Oriowo, 2006). In this work 8-Br-cAMP, another cAMP analog, was used to assess the role of the PKA activation and a possible downstream modulation of the KV channels, which would lead VSM relaxation, bypassing the direct activation of AC by FSK.
The association of remotely-sensed outdoor temperature with blood pressure levels in REGARDS: A cross-sectional study of a large, national cohort of African-American and white participants
2011, Environmental Health: A Global Access Science SourceIsoproterenol inhibits angiotensin II-stimulated proliferation and reactive oxygen species production in vascular smooth muscle cells through heme oxygenase-1
2009, Biological and Pharmaceutical Bulletin