Guanylyl cyclase inhibition reduces contractility and decreases cGMP and cAMP in isolated rat hearts

Objectives of the current studies were to characterize the pattern of GnRH secretion in the cerebrospinal fluid of the bovine third ventricle, determine its correspondence with the tonic and surge release of LH in ovariectomized cows, and examine the dynamics of GnRH pulse generator activity in response to known modulators of LH release (suckling; neuropeptide Y [NPY]). In ovariectomized cows, both tonic release patterns and estradiol-induced surges of GnRH and LH were highly correlated (0.95; p < 0.01). Collectively, LH pulses at the baseline began coincident with (84%) or within one sampling point after (100%) the onset of a GnRH pulse, and all estradiol-induced LH surges were accompanied by corresponding surges of GnRH. A 500- microg dose of NPY caused immediate cessation of LH pulses and lowered (p < 0.001) plasma concentrations of LH for at least 4 h. This corresponded with declines (p < 0.05) in both GnRH pulse amplitude and frequency, but GnRH pulses were completely inhibited for only 1.5-3 h. In intact, anestrous cows, GnRH pulse frequency did not differ before and 48-54 h after weaning on Day 18 postpartum, but concentrations of GnRH (p < 0.05) and amplitudes of GnRH pulses (4 of 7 cows) increased in association with weaning and heightened secretion of LH. We conclude that the study of GnRH secretory dynamics in third-ventricle CSF provides a reasonable approach for examining the activity and regulation of the hypothalamic pulse generator in adult cattle. However, data generated using this approach must be interpreted in their broadest context. Although strong neurally mediated inhibitors of LH pulsatility (suckling; NPY) had robust effects on one or more GnRH secretory characteristics in CSF, only high doses of NPY briefly abolished GnRH pulses. This implies that the GnRH signal received at the hypophyseal portal vessels under these conditions may differ quantitatively or qualitatively from those in CSF, and theoretically would be undetectable or below a biologically effective threshold when LH pulses are absent.