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).

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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