Angiotensin and atrial natriuretic peptides generally act to oppose each other. Angiotensin II has strong acute vascular effects and is an important mediator of renal Na+ retention. Atrial natriuretic peptides are released from the atria of the heart by distention and enhance renal Na+ excretion. Angiotensin works through the cAMP second messenger, and atrial natriuretic peptides works through cGMP.
The enzyme renin is synthesized and stored in the juxtaglomerular cells of the renal afferent arteriole. Renin is released by a variety of stimuli including decreased Na+ delivery to the macula densa, decreased renal perfusion pressure, increased sympathetic nerve activity secondary to arterial hypotension, and P-adrenergic agonists, such as epinephrine.
Renin acts on the plasma protein angiotensinogen (renin substrate) to form angiotensin I. Angiotensin I is hydrolyzed to angiotensin II by angiotensin-converting enzyme (ACE), found in high concentrations in the pulmonary epithelium. Angiotensin is rapidly degraded by peptidases collectively called angiotensinases. Angiotensin II can also be formed locally in the brain and in the kidney, independently of the plasma conversion process.
Acutely, angiotensin is a potent constrictor of vascular smooth muscle. Consequently, angiotensin II increases total peripheral resistance and therefore arterial blood pressure. Angiotensin II also causes venoconstriction, which enhances cardiac output.
Angiotensin promotes renal retention of Na+ and water. Efferent arteriolar constriction acts to increase GFR but also increases peritubular fluid reabsorption. Angiotensin II also enhances proximal tubule Na+ reabsorption and acutely increases aldosterone release, which augments renal Na+ reabsorption. Angiotensin stimulates ADH release from the posterior pituitary and acts in the central nervous system to increase thirst.
Atrial myocytes synthesize and store a class of peptides collectively called atrial natriuretic peptides. Stretch of the myocytes, as occurs with volume overloading, stimulates secretion of atrial natriuretic peptides.
The physiologic importance of atrial natriuretic peptides is not yet established. Acutely, atrial natriuretic hormone acts to increase renal Na+ excretion. Atrial natriuretic peptides dilate renal afferent and efferent arterioles and increase glomerular filtration rate. Atrial natriuretic peptides decrease renin release, inhibit antidiuretic hormone secretion, and decrease Na+ reabsorption in the renal collecting duct. The natriuresis caused by atrial natriuretic peptides decreases plasma volume.
Prostaglandins (PGs), thromboxanes, and leukotrienes are three classes of arachidonic acid derivatives collectively called eicosanoids. The primary prostaglandins of biological interest are prostaglandin E2 and F2a.Arachidonic acid for the synthesis of these two eicosanoids is obtained from the plasma membrane.
Cyclooxygenase converts arachidonic acid to prostaglandins G2 and H2. Thromboxane synthase converts PGH2 to thromboxanes A2 and A3. Prostacyclin synthase converts PGH2 to PGI2. Prostaglandins E1 and E3 are derived from precursors similar, but not identical, to arachidonic acid. Lipoxygenase converts arachidonic acid to leukotrienes.
Prostaglandins have diverse intracellular, local, and endocrine effects. Thromboxane A2, prostaglandin F2a, and leukotrienes C4 and D4 constrict pulmonary airway smooth muscle, and prostaglandin E2 dilates airway smooth muscle. Platelet aggregation is enhanced by thromboxane A2 but inhibited by prostacyclin. Thromboxane A2 is the primary pulmonary vasoconstrictor, and prostacyclin (prostaglandin I2) is a pulmonary vasodilator. Hemorrhage (sympathetics and angiotensin II) causes renal formation of vasodilator prostaglandins PGE2 and PGI2.
Endorphins, enkephalins, and dynorphin are powerful peptide or polypeptide analgesics. Their analgesic action requires binding to opiate receptors on nerve cells. Naloxone antagonizes the action of these opiate agonists.
The prohormone containing endorphin also contains ACTH and melanocyte-stimulating hormone. Enkephalins are small peptides that can serve as neurotransmitters in the brain. Enkephalins act to attenuate substance P release in the dorsal horn of the spinal cord and inhibit afferent pain fibers. Opiates inhibit transmission at sympathetic and locus caeruleus synapses. Dynorphins and other endorphins contain an enkephalin sequence on the amino terminal end of the peptide.