Salt-induced sympathoexcitation involves vasopressin V1a receptor activation in the paraventricular nucleus of the hypothalamus.
A high-salt diet can lead to hydromineral imbalance and increases in plasma sodium and osmolality. It is recognized as one of the major contributing factors for cardiovascular diseases such as hypertension. The paraventricular nucleus (PVN) plays a pivotal role in osmotically driven sympathoexcitation and high blood pressure, the precise mechanisms of which are not fully understood. Recent evidence indicates that AVP released from magnocellular neurons might be involved in this process. Using a combination of in vivo and in situ studies, we sought to investigate whether AVP, acting on PVN neurons, can change mean arterial pressure (MAP) and sympathetic nerve activity (SNA) in euhydrated male rats. Furthermore, we wanted to determine whether V1a receptors on PVN neurons would be involved in salt-induced sympathoexcitation and hypertension. In rats, 4 days of salt loading (NaCl 2%) elicited a significant increase in plasma osmolality (39 ± 7 mosmol/kgH2O), an increase in MAP (26 ± 2 mmHg, P < 0.001), and sympathoexcitation compared with euhydrated rats. Microinjection of AVP into the PVN of conscious euhydrated animals (100 nl, 3 μM) elicited a pressor response (14 ± 2 mmHg) and a significant increase in lumbar SNA (100 nl, 1 mM) (19 ± 5%). Pretreatment with a V1a receptor antagonist, microinjected bilaterally into the PVN of salt-loaded animals, elicited a decrease in lumbar SNA (-14 ± 5%) and MAP (-19 ± 5 mmHg), when compared with the euhydrated group. Our findings show that AVP plays an important role in modulating the salt-induced sympathoexcitation and high blood pressure, via V1a receptors, within the PVN of male rats. As such, V1a receptors in the PVN might contribute to neurogenic hypertension in individuals consuming a high-salt diet.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Natalia
N
Ribeiro
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Helena do Nascimento
Hdo N
Panizza
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Karoline Martins Dos
KM
Santos
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Hildebrando C
HC
Ferreira-Neto
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil antunes@icb.usp.br.
Vagner Roberto
VR
Antunes
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists / Q000008:administration & dosage; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000378:metabolism*; D062186:Arterial Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006973:Hypertension / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D008845:Microinjections; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000819:agonists / Q000378:metabolism*; D017673:Sodium Chloride, Dietary; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors
D065092:Antidiuretic Hormone Receptor Antagonists; D017483:Receptors, Vasopressin; D017673:Sodium Chloride, Dietary; C582098:V1a vasopressin receptor, rat; D001127:Arginine Vasopressin
hypertension; paraventricular nucleus of the hypothalamus; salt loading; sympathoexcitation; vasopressin