Influx of extracellular Ca2+
Activation of NADP/NADPH oxidase
Modulation of translation efficiency
Activation of inducible transcription factors
Activation of small G proteins
Activation of phospholipases
Mobilization of intracellular
Activation of MAP kinases
Activation of Jak/Stat pathways
Activation of non-receptor tyrosine kinases
Modulation of Ser/Thr protein kinases
FIGURE 30-3 Multiple mechanisms of AT1 receptor—effector coupling. ATX receptors couple to Gq, Gp and G 12/13. Through effectors, second messengers, and signaling cascades, a large array of response pathways is subsequently engaged to produce immediate and long-term effects of Angll.
normal within minutes. This rapid pressor response to Angll is due to a swift increase in total peripheral resistance—a response that helps to maintain arterial blood pressure in the face of blood loss or vasodilation. Although Angll increases cardiac contractility directly via voltage-gated Ca2+ channels and increases heart rate indirectly (via facilitation of sympathetic tone, enhanced adrenergic neurotransmission, and adrenal catecholamine release), the rapid increase in arterial blood pressure activates a baroreceptor reflex that decreases sympathetic tone and increases vagal tone. Thus, depending on the physiological state, Angll may increase, decrease, or not change cardiac contractility, heart rate, and cardiac output. Changes in cardiac output therefore contribute little, if at all, to the rapid pressor response induced by Angll.
Angll also causes a slow pressor response that chronically helps to maintain blood pressure. Continuous infusion of initially subpressor doses of Angll gradually increases blood pressure over a period of days. This slow pressor response probably is mediated by decreases in renal excretion that shift the renal pressure-natriuresis curve to the right (see below). Angll stimulates the synthesis of endothelin-1 and superoxide anion, which may contribute to the slow pressor response. In addition to its effects on arterial blood pressure, Angll causes hypertrophy of vascular and cardiac cells and increased collagen deposition by cardiac fibroblasts. The effects of Angll on total peripheral resistance, renal function, and cardiovascular structure are mediated by direct and indirect mechanisms (see Figure 30-4).
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