Induction of hypertension blunts baroreflex inhibition of vasopressin neurons in the rat.
Vasopressin secretion from the posterior pituitary gland is determined by action potential discharge of hypothalamic magnocellular neurosecretory cells. Vasopressin is a potent vasoconstrictor, but vasopressin levels are paradoxically elevated in some patients with established hypertension. To determine whether vasopressin neurons are excited in hypertension, extracellular single-unit recordings of vasopressin neurons from urethane-anaesthetized Cyp1a1-Ren2 rats with inducible angiotensin-dependent hypertension were made. The basal firing rate of vasopressin neurons was higher in hypertensive Cyp1a1-Ren2 rats than in non-hypertensive Cyp1a1-Ren2 rats. The increase in firing rate was specific to vasopressin neurons because oxytocin neuron firing rate was unaffected by the induction of hypertension. Intravenous injection of the α1-adrenoreceptor agonist, phenylephrine (2.5 μg/kg), transiently increased mean arterial blood pressure to cause a baroreflex-induced inhibition of heart rate and vasopressin neuron firing rate (by 52 ± 9%) in non-hypertensive rats. By contrast, intravenous phenylephrine did not inhibit vasopressin neurons in hypertensive rats, despite a similar increase in mean arterial blood pressure and inhibition of heart rate. Circulating angiotensin II can excite vasopressin neurons via activation of afferent inputs from the subfornical organ. However, the increase in vasopressin neuron firing rate and the loss of inhibition by intravenous phenylephrine were not blocked by intra-subfornical organ infusion of the angiotensin AT1 receptor antagonist, losartan. It can be concluded that increased vasopressin neuron activity at the onset of hypertension is driven, at least in part, by reduced baroreflex inhibition of vasopressin neurons and that this might exacerbate the increase in blood pressure at the onset of hypertension.
Centre for Neuroendocrinology, University of Otago, Dunedin, 9054, New Zealand.|Department of Physiology, University of Otago, Dunedin, 9054, New Zealand.
Su Young
SY
Han
Centre for Neuroendocrinology, University of Otago, Dunedin, 9054, New Zealand.|Department of Physiology, University of Otago, Dunedin, 9054, New Zealand.
Gregory T
GT
Bouwer
Centre for Neuroendocrinology, University of Otago, Dunedin, 9054, New Zealand.|Department of Physiology, University of Otago, Dunedin, 9054, New Zealand.
Alexander J
AJ
Seymour
Centre for Neuroendocrinology, University of Otago, Dunedin, 9054, New Zealand.|Department of Physiology, University of Otago, Dunedin, 9054, New Zealand.
Aaron K
AK
Korpal
Department of Physiology, University of Otago, Dunedin, 9054, New Zealand.
Daryl O
DO
Schwenke
Centre for Neuroendocrinology, University of Otago, Dunedin, 9054, New Zealand.|Department of Physiology, University of Otago, Dunedin, 9054, New Zealand.
Colin H
http://orcid.org/0000-0003-2305-846X
CH
Brown
D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D055647:Rats, Transgenic; D013356:Subfornical Organ / Q000187:drug effects / Q000502:physiology; D014667:Vasopressins / Q000502:physiology*
D058646:Adrenergic alpha-1 Receptor Agonists; D047228:Angiotensin II Type 1 Receptor Blockers; D014667:Vasopressins; D010656:Phenylephrine; D019808:Losartan
blood pressure; oxytocin; subfornical organ; supraoptic nucleus