Adenosine receptor heart rate

Increased delivery of salt to the TAL leads to activation of the macula densa and a reduction in glomerular filtration rate (GFR) by tubuloglomerular (TG) feedback. The mechanism of this feedback is secretion of adenosine by macula densa cells, which locally causes afferent arteriolar vasoconstriction. This vasoconstriction reduces GFR. Tubuloglomerular feedback-mediated reduction in GFR exacerbates the reduction that was initially caused by decreased cardiac output. Recent work with adenosine receptor antagonists (eg, rolofylline) has shown that it will soon be possible to circumvent this complication of diuretic therapy in heart failure patients. Using rolofylline with a diuretic will make it possible to produce an effective diuresis in patients with heart failure without causing renal decompensation. 

Cross HR, Murphy E, Black RG, Auchampach JA, Steenbergen C (2002) Overexpression of A3 adenosine receptors decreases heart rate, preserves energetics, and protects ischemic hearts. Am J Physiol Heart Circ Physiol 283 1562-1568... 

Theophylline, a methylxanthine, relaxes bronchial muscle, although its precise mode of action is still debated. Inhibition of phosphodiesterase (PDE), especially its type 4 isoform now seems the most likely explanation for its bronchodilator and more recently reported anti-inflammatory effects. Blockade of adenosine receptors is probably unimportant. Other actions of theophylline include chronotropic and inotropic effects on the heart and a direct effect on the rate of urine production (diuresis). 

Pseudoephedrine is a weak base (pK, 9.4) that stimulates both a- and jS-adrenergic receptors, as well as the release of neuronal norepinephrine. fil stimulation produces increased heart rate and blood pressure. The a-adrenergic effects are believed to result from the reduced production of cyclic adenosine-3, 5 -monophosphate (cyclic 3, 5 -AMP) by inhibition of the enzyme adenyl cyclase, whereas S-adrenergic effects appear to be caused by the stimulation of adenyl cyclase activity. 

P. H. Van der Graaf, E. A. Van Schaick, R. A. Mathot, A. P. Ijzerman, and M. Danhof, Mechanism-based pharmacokinetic-pharmacodynamic modeling of the effects of N6-cyclopentyladenosine analogs on heart rate in rat estimation of in vivo operational affinity and efficacy at adenosine A1 receptors. J Pharmacol Exp Ther 283 809-816... 

The rise in heart rate (Fig. 4b) observed within the first minutes of infusion is probably best described as a reflex tachycardia. The same phenomenon has also been observed with the Aj -selective full agonist CGS 21680. The latter compound, however, reached peak values (data not shown) as high as 550 beats per minute (bpm), contrasting to the mean highest value for theophylline-7-riboside of 425 bpm. CPA in the same experimental setup caused a decrease in heart rate to as low as 150 bpm. Thus, theophylline-7-riboside behaved as a partial agonist on parameters that are strictly A, receptor mediated (heart rate) or both A and Aj (mean arterial pressure). In conclusion, theophylline-7-riboside, developed from the antagonist theophylline, may be a useful tool as a partial agonist for adenosine receptors. Its low affinity is a potential drawback, which warrants the development of other compounds for which theophylline-7-riboside may be a lead. 

Coronary blood flow is enhanced by Epi or by cardiac sympathetic stimulation under physiological conditions. The increased flow, which occurs even with doses that do not increase the aortic blood pressure, is the result of two factors. The first is the increased relative duration of diastole at higher heart rates (see below) this is partially offset by decreased blood flow during systole because of more forceful contraction of the surrounding myocardium and an increase in mechanical compression of the coronary vessels. The increased flow during diastole is further enhanced if aortic blood pressure is elevated by Epi as a consequence, total coronary flow may be increased. The second factor is a metabolic dilator effect that results from the increased strength of contraction and myocardial consumption due to direct effects of Epi on cardiac myocytes. This vasodilation is mediated in part by adenosine released from cardiac myocytes, which tends to override a direct vasoconstrictor effect of Epi that results from activation of a receptors in coronary vessels. 

Figure 2 Relationship between the developmental profiles for the maximal sensitivity to 2-ClA-induced inhibition of atrial beating rate and the maximum number (Bmax) of Aj adenosine receptors labeled by [ HJDPCPX in embryonic chick heart membranes. Values for 2-ClA-induced suppression of atrial beating rate and [ H]DPCPX Bmax were normalized to the percentage of the maximal value obtained for each parameter during embryogenesis. The normalized values for [ HJDPCPX Bmax for each embryonic age depicted were calculated as the percentage of the value obtained on embryonic day 9 (74.8 6.5 fmol/mg protein), while values for sensitivity to 2-ClA-induced negative chronotropy are the percentages of the maximum response which was a complete suppression of beating rate.

Adenosine A2A receptor CNS, CV Hypotension, heart rate changes, locomotor activity, platelet aggregation... 

Answer D. An increase in AV conduction is characteristic of quinidine, which exerts quite marked blocking actions on muscarinic receptors in the heart. Thus, an atrial rate, formerly transmitted to the ventricles in a 2 1 ratio, may be transmitted in a 1 1 ratio after quinidine. This effect of quinidine can be offset by the prior administration of an antiar-rhythmic drug that decreases AV nodal conduction, such as digoxin or verapamil. All of the drugs listed (except quinidine) slow AV nodal conduction, but adenosine and esmolol (a beta blocker) are very short-acting agents used IV only. 

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