deoxycortone-pivalate and Hypertension

Increasing evidence demonstrates that circadian clock proteins are important regulators of physiological functions including blood pressure. An established risk factor for developing cardiovascular disease is the absence of a blood pressure dip during the inactive period. The goal of the present study was to determine the effects of a high salt diet plus mineralocorticoid on PER1-mediated blood pressure regulation in a salt-resistant, normotensive mouse model, C57BL/6J.. Blood pressure was measured using radiotelemetry. After control diet, wild-type (WT) and Per1 (KO) knockout mice were given a high salt diet (4% NaCl) and the long-acting mineralocorticoid deoxycorticosterone pivalate. Blood pressure and activity rhythms were analysed to evaluate changes over time.. Blood pressure in WT mice was not affected by a high salt diet plus mineralocorticoid. In contrast, Per1 KO mice exhibited significantly increased mean arterial pressure (MAP) in response to a high salt diet plus mineralocorticoid. The inactive/active phase ratio of MAP in WT mice was unchanged by high salt plus mineralocorticoid treatment. Importantly, this treatment caused Per1 KO mice to lose the expected decrease or 'dip' in blood pressure during the inactive compared to the active phase.. Loss of PER1 increased sensitivity to the high salt plus mineralocorticoid treatment. It also resulted in a non-dipper phenotype in this model of salt-sensitive hypertension and provides a unique model of non-dipping. Together, these data support an important role for the circadian clock protein PER1 in the modulation of blood pressure in a high salt/mineralocorticoid model of hypertension.

Topics: Animals; Blood Pressure; Desoxycorticosterone; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Hypertension; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mineralocorticoids; Period Circadian Proteins; Real-Time Polymerase Chain Reaction; Sodium Chloride, Dietary

The effects of increased dietary calcium intake on blood pressure and arterial function were investigated in one-kidney deoxycorticosterone-salt hypertensive Wistar rats. The calcium content of the control diet was 1.1%, and that of the high calcium diet, 2.5%. During the 10-week study calcium supplementation markedly attenuated the steroid-salt-induced rise in blood pressure and the associated cardiac hypertrophy. Responses of mesenteric arterial rings in vitro were examined at the end of the study. In deoxycorticosterone-salt-treated rats, the contractile sensitivity of endothelium-denuded preparations to norepinephrine, 5-hydroxytryptamine, and KCl, and the inhibitory effect of nifedipine on KCl-evoked responses were enhanced. It is interesting that the high calcium diet alleviated the steroid-salt-induced increase in sensitivity to KCl but did not significantly affect it to the receptor-mediated agonists norepinephrine and 5-hydroxytryptamine. Thus, sensitivity to membrane depolarization was reduced by calcium supplementation. Smooth muscle responses were also studied by challenging the preparations with KCl in a calcium-free solution, after which calcium was added to the organ bath in increasing concentrations. In steroid-salt-treated rats, these calcium contractions were attenuated, but concomitant calcium supplementation normalized the responses, suggesting improved cell membrane handling of calcium. In addition, the mineralocorticoid-salt treatment impaired relaxation responses of endothelium-intact arterial rings to acetylcholine, sodium nitroprusside, and isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acetylcholine; Animals; Blood Pressure; Calcium; Calcium, Dietary; Cardiomegaly; Desoxycorticosterone; Endothelium, Vascular; Hypertension; In Vitro Techniques; Isoproterenol; Male; Mesenteric Arteries; Nitroprusside; Norepinephrine; Potassium Chloride; Rats; Rats, Wistar; Serotonin; Sodium Chloride; Vasoconstriction

Dietary sodium and the myocardial alpha 1-receptor have been implicated in the hypertrophic response of myocardial tissue. Alterations in sodium homeostasis have been demonstrated to influence sympathetic nervous function, centrally and peripherally. In this investigation, we have examined the effect of dietary sodium on the development of myocardial hypertrophy; and the role of sympathetic neuroeffector mechanisms in the hypertrophic response. Studies were performed in three groups of uninephrectomized rats: A-regular diet; B-1% saline/regular diet; C-1% Saline/doca/regular diet. Groups A and B did not develop systemic hypertension (SHT). Saline treatment increased heart weight and the density of surface alpha 1-receptors; myocardial norepinephrine (NE) was reduced. Group C developed SHT. Heart weight was greatest in Group C; and myocardial NE was severely depleted. Downregulation of myocardial alpha 1-receptors, a finding consistent with the hyperadrenergic state, was observed in Group C. Our results suggest dietary sodium may modulate hypertrophic response in myocardial tissue, by altering sympathetic neuroeffector mechanisms.

Topics: Animals; Blood Pressure; Cardiomegaly; Desoxycorticosterone; Hypertension; Iodine Radioisotopes; Male; Myocardium; Norepinephrine; Organ Size; Rats; Rats, Inbred Strains; Receptors, Adrenergic, alpha; Sodium, Dietary; Sympathetic Nervous System

Topics: Addison Disease; Adrenal Cortex; Adrenal Cortex Diseases; Desoxycorticosterone; Hypertension; Kidney