Adrenoceptor activation, consequences

TRP6-specific antisense oligonucleotides, and consequently, cationic current and Ba2+ influx evoked in response to oq -adrenoceptor activation were both greatly attenuated. Importantly, Ba2+ influx induced by thapsigargin, which is an indication of store operated divalent cation entry, was not significantly affected... 

Vascular smooth muscle tone is regulated by adrenoceptors consequently, catecholamines are important in controlling peripheral vascular resistance and venous capacitance. Alpha receptors increase arterial resistance, whereas 2 receptors promote smooth muscle relaxation. There are major differences in receptor types in the various vascular beds (Table 9-4). The skin vessels have predominantly receptors and constrict in the presence of epinephrine and norepinephrine, as do the splanchnic vessels. Vessels in skeletal muscle may constrict or dilate depending on whether ffor 13 receptors are activated. Consequently, the overall effects of a sympathomimetic drug on blood vessels depend on the relative activities of that drug at and 8receptors and the anatomic sites of the vessels affected. In addition, Di receptors promote vasodilation of renal, splanchnic, coronary, cerebral, and perhaps other resistance vessels. Activation of the Di receptors in the renal vasculature may play a major role in the natriuresis induced by pharmacologic administration of dopamine. 

The decreased work capacity of the in-farcted myocardium leads to a reduction in stroke volume (SV) and hence cardiac output (CO). The fall in blood pressure (RR) triggers reflex activation of the sympathetic system. The resultant stimulation of cardiac 3-adreno-ceptors elicits an increase in both heart rate and force of systolic contraction, which, in conjunction with an a-adren-oceptor-mediated increase in peripheral resistance, leads to a compensatory rise in blood pressure. In ATP-depleted cells in the infarct border zone, resting membrane potential declines with a concomitant increase in excitability that may be further exacerbated by activation of p-adrenoceptors. Together, both processes promote the risk of fatal ventricular arrhythmias. As a consequence of local ischemia, extracellular concentrations of H+ and K+ rise in the affected region, leading to excitation of nociceptive nerve fibers. The resultant sensation of pain, typically experienced by the patient as annihilating, reinforces sympathetic activation. 

The hemodynamic effects of sotalol are related to its 3-adrenoceptor antagonist activity. Accordingly, decreases in resting heart rate and in exercise-induced tachycardia are seen in patients receiving sotalol. A modest reduction in systolic pressure and in cardiac output may occur. The reduction in cardiac output is a consequence of lowering the heart rate, since stroke volume is unaffected by sotalol treatment. In patients with normal ventricular function, cardiac output is maintained despite the decrease in heart rate because of the simultaneous increase in the stroke volume. 

Symptoms include a severe, sudden throbbing headache with slow palpitation, flushing, visual disturbance, nausea, vomiting and severe hypertension. If headache occurs without hypertension it may be due to histamine release. The hypertension is due both to vasoconstriction from activation of a-adrenoceptors and to increased cardiac output consequent on activation of cardiac P-adrenoceptors. The mechanism is thus similar to that of the episodic hypertension in a patient with phaeochro-moc5doma. The rational and effective treatment is an a-adrenoceptor blocker (phentolamine, 5 mg i.v.) and a P-blocker may be later added in case of excessive tachycadia. 

X,-Adrenoceptors occur on noradrenergic nerve terminals. Their activation by norepinephrine inhibits adeny lyl cyclase. The consequent fall in cAMP doses Ca channels and diminishes further transmitter release. 

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