ABSTRACT
The present experiments were conducted to investigate the role of the alpha(1A)-, alpha(1B), beta(1)- and beta(2)-adrenoceptors of the lateral hypothalamus (LH) on the water and salt intake responses elicited by subfornical organ (SFO) injection of angiotensin II (ANG II) in rats. 5-methylurapidil (an alpha(1A)-adrenergic antagonist), cyclazosin (an alpha(1B)-adrenergic antagonist) and ICI-118,551 (a beta(2)-adrenergic antagonist) injected into the LH produced a dose-dependent reduction, whereas efaroxan (an alpha(2)-antagonist) increased the water intake induced by administration of ANG II into the SFO. These data show that injection of 5-methylurapidil into the LH prior to ANG II into the SFO increased the water and sodium intake induced by the injection of ANG II. The present data also show that atenolol (a beta(1)-adrenergic antagonist), ICI-118,551, cyclazosin, or efaroxan injected into the LH reduced in a dose-dependent manner the water and sodium intake to angiotensinergic activation of SFO. Thus, the alpha(1)- and beta-adrenoceptors of the LH are possibly involved with central mechanisms dependent on ANG II and SFO that control water and sodium intake.
Subject(s)
Angiotensin II/pharmacology , Drinking/drug effects , Hypothalamic Area, Lateral/drug effects , Receptors, Adrenergic, alpha/drug effects , Receptors, Adrenergic, beta/drug effects , Sodium Chloride, Dietary , Vasoconstrictor Agents/pharmacology , Adrenergic alpha-Antagonists/pharmacology , Adrenergic beta-Antagonists/pharmacology , Animals , Drinking/physiology , Hypothalamic Area, Lateral/physiology , Male , Rats , Rats, Sprague-Dawley , Receptors, Adrenergic, alpha/physiology , Receptors, Adrenergic, beta/physiology , Subfornical Organ/drug effects , Subfornical Organ/physiologyABSTRACT
The effects of clonidine on sodium and potassium excretions were examined after previous administration of prazosin (an alpha 1-adrenergic receptor antagonist) and yohimbine (an alpha 2-adrenergic receptor antagonist) into the ventromedial nucleus of the hypothalamus of conscious rats. Clonidine injected into the ventromedial nucleus of the hypothalamus induced inhibitory and facilitatory effects on the urinary sodium and potassium excretions. The results suggest that facilitatory effects of clonidine on natriuresis and kaliuresis are mediated through activation of alpha 1-adrenoceptors and that inhibitory effects require alpha 2A-adrenoceptors.
Subject(s)
Clonidine/pharmacology , Hypothalamus/drug effects , Kidney/drug effects , Potassium/urine , Sodium/urine , Adrenergic alpha-Antagonists/pharmacology , Animals , Dose-Response Relationship, Drug , Hypothalamus/metabolism , Kidney/physiology , Male , Prazosin/pharmacology , Rats , Yohimbine/pharmacologyABSTRACT
We determined the effects of two classical angiotensin II (ANG II) antagonists, [Sar1, Ala8]-ANG II and [Sar1, Thr8]-ANG II, and losartan (a nonpeptide and selective antagonist for the AT1 angiotensin receptors) on diuresis, natriuresis, kaliuresis and arterial blood pressure induced by ANG II administration into the median preoptic nucleus (MnPO) of male Holtzman rats weighing 250-300 g. Urine was collected in rats submitted to a water load (5% body weight) 1 h later. The volume of the drug solutions injected was 0.5 microliters over 10-15 s. Pre-treatment with [Sar1, Ala8]-ANG II (12 rats) and [Sar1, Thr8]-ANG II (9 rats), at the dose of 60 ng reduced (13.7 +/- 1.0 vs 11.0 +/0 1.0 and 10.7 +/0 1.2, respectively), whereas losartan (14 rats) at the dose of 160 ng totally blocked (13.7 +/- 1.0 vs 7.6 +/- 1.5) the urine excretion induced by injection o 12 ng of ANG II (14 rats). [Sar1, Ala8]-ANG II impaired Na+ excretion (193 +/- 16 vs 120 +/- 19), whereas [Sar1, Thr8]-ANG II and losartan block Na+ excretion (193 +/- 16 vs 77 +/- 15 and 100 +/- 12, respectively) induced by ANG II. Similar effects induced by ANG II on K+ excretion were observed with [Sar1, Ala8]-ANG II, [Sar1, Thr8]- ANG II, and losartan pretreatment (133 +/- 18 vs 108 +/- 11, 80 +/- 12, and 82 +/- 15, respectively). The same doses as above of [Sar1, Ala8]-ANG II (8 rats), [Sar1, Thr8]-ANG II (8 rats), and losartan (9 rats) blocked the increase in the arterial blood pressure induced by 12 ng of ANG II (12 rats) (32 +/- 4 vs 4 +/- 2, 3.5 +/- 1, and 2 +/- 1, respectively. The results indicate that the AT1 receptor subtype participates in the increases of diuresis, natriuresis, kaliuresis and arterial blood pressure induced by the administration of ANG II into the MnPO.
Subject(s)
Angiotensin II/pharmacology , Blood Pressure/drug effects , Diuresis/drug effects , Natriuresis/drug effects , Potassium/urine , Preoptic Area/drug effects , Receptors, Angiotensin/drug effects , Angiotensin II/antagonists & inhibitors , Angiotensin Receptor Antagonists , Animals , Antihypertensive Agents/pharmacology , Biphenyl Compounds/pharmacology , Imidazoles/pharmacology , Losartan , Male , Preoptic Area/physiology , Rats , Rats, Sprague-Dawley , Receptors, Angiotensin/physiology , Tetrazoles/pharmacologyABSTRACT
We determined the effects of two classical angiotensin II (ANG II) antagonists, [Sar1, Ala8]-ANG II and [Sar1, Thr8]-ANG II, and losartan (a nonpeptide and selective antagonist for the AT1 angiotensin receptors) on diuresis, natriuresis, kaliuresis and arterial blood pressure induced by ANG II administration into the median preoptic nucleus (MnPO) of male Holtzman rats weighing 250-300 g. Urine was colected in rats submitted to a water load (5 percent body weight) by gastric gavage, followed by a second water load (5 percent body weight) 1 h later. The volume of the drug solutions injected was 0.5 µl over 10-15 s. Pre-treatment with [Sar1, Ala8]-ANG II (12 rats) and [Sar1, Thr8]-ANG II (9 rats), at the dose of 60 ng reduced (13.7 +/- 1.0 vs 11.0 +/- 1.0 +/- 1.2, respectively), whereas losartam (14 rats) at the dose of 160 ng totally blocked (13.7 +/- 1.0 vs.7.6 +/- 1.5) the urine excretion induced by injection of 12 ng of ANG II (14 rats)...