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Abstract-␣-Calcitonin gene-related peptide (␣CGRP) is a pleiotropic neuropeptide implicated in a variety of physiological processes. To better understand the biological functions of ␣CGRP, we developed an ␣CGRP-null mouse model using a gene targeting approach. Recordings of mean arterial pressure (MAP) and heart rate (HR) showed that basal MAP and HR were significantly higher in both anesthetized and conscious, unrestrained ␣CGRP-null mice than in corresponding wild-type mice. The elevated MAP in ␣CGRP-null mice was shown to be the result of elevated peripheral vascular resistance by ␣-adrenergic blockade with prazosin and by transthoracic echocardiogram, which revealed no significant differences between ␣CGRP-null and wild-type mice in the stroke volume, fractional shortening, and ejection fraction. Moreover, evaluation of autonomic nervous activity by measuring HR after pretreatment of atropine and/or atenolol and by analyzing arterial baroreceptor reflexes showed sympathetic nervous activity to be significantly elevated in ␣CGRP-null mice; elevated levels of urinary catecholamine metabolites and decreased HR variability in mutant mice were also consistent with that finding. These findings suggest that ␣CGRP contributes to the regulation of cardiovascular function through inhibitory modulation of sympathetic nervous activity. Key Words: calcitonin gene-related peptide Ⅲ gene targeting Ⅲ blood pressure Ⅲ autonomic nervous system Ⅲ hypertension C alcitonin gene-related peptide (CGRP) is a 37-amino acid vasoactive neuropeptide produced by tissue-specific alternative splicing of the primary transcript of the calcitonin/ ␣CGRP gene. 1 While calcitonin (CT), which controls calcium homeostasis, is expressed almost exclusively in the C cells of the thyroid gland, ␣CGRP is widely distributed in the central and peripheral nervous systems in mammals. In addition, a second CGRP isoform, ␤CGRP, is encoded by a different gene locus and is expressed almost exclusively in specific neuronal sites. 2 These two CGRP isoforms-␣ and ␤ in rat and I and II in humans-exhibit overlapping biological activities in most vascular beds. 3 Within the nervous system, CGRP immunoreactivity has been detected in spinal cord motor neurons, dorsal root ganglia, and motor nerve endings. 4 Other neuropeptides, the tachykinins, which include substance P (SP) and neurokinin A (NKA), exhibit similar expression patterns to ␣CGRP in several regions of the nervous system. ␣CGRP and tachykinins coexist in primary afferent neurons, forming the part of the so-called nonadrenergic, noncholinergic (NANC) nervous system, 5 and their release from sensory pain fibers has been implicated in the perception of pain.NANC neurons containing ␣CGRP are also widely distributed among autonomic fibers innervating the vasculature; for example, they are found in blood vessels at the junction of the adventitia and the media passing into the muscle layer. 5 Moreover, ␣CGRP is a potent vasodilator, 6 and several investigators have claimed that ␣CGRP may play a key role in regu...

A chronic increase in vascular AM production reduces BP at least in part via an NO-dependent pathway. In addition, smaller responses to LPS in transgenic mice suggest that AM is protective against the circulatory collapse, organ damage, and mortality characteristic of endotoxic shock.

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The dimensions of the 10 triangles around the cavernous sinus were measured to define the anatomical characteristics of the triangles and to compare their consistency in shape and area. Twelve tissue blocks containing the bilateral cavernous sinuses and medial two-thirds of the middle cranial fossae were obtained from Japanese adults at autopsy, fixed to a stereotactic frame, and examined with an operative microscope. The dimensions of each triangle were measured with calipers and compared, based on the same point and border. The anteromedial triangle and the superolateral (Parkinson's) triangle were more consistent in shape than the paramedial and oculomotor triangles, but the oculomotor triangle was larger in area than these other triangles. The posteromedial (Kawase's) triangle was more consistent in shape and larger than the anterolateral, lateral, and the posterolateral (Glasscock's) triangles. The anteromedial and superolateral (Parkinson's) triangles are important for the combined epi- and subdural approach to cavernous sinus lesions. The posteromedial (Kawase's) triangle is important for gaining access to the posterior cranial fossa from the middle cranial fossa.