cyclic-gmp and cirazoline

1. We have investigated the in vitro interaction between chloride ions and endothelium as revealed by alterations in vascular contractility and smooth muscle cell membrane potential in isolated pulmonary arteries from Dahl salt-resistant normotensive and salt-sensitive hypertensive rats. 2. Exposure to nitro-l-arginine methyl ester (l-NAME) of tissues from normotensive but not hypertensive rats augmented contractions to cirazoline. While chloride removal did not alter cirazoline-induced contractions, it completely abolished the augmentation by l-NAME in normotensive rats. However, in hypertensive rats, removal of chloride ions significantly attenuated contractions elicited by cirazoline, and l-NAME effectively reversed this inhibition. 3. Methacholine-induced endothelium-dependent relaxations of the same magnitude were evident in both normotensive and hypertensive rats. However, basal cyclic GMP levels were found to be significantly higher (7.8-fold) in blood vessels of normotensive rats compared to hypertensive rats. 4. The resting membrane potential in pulmonary arteries of hypertensive rats (-52.1+/-1.04 mV) revealed a significant hyperpolarisation when compared with that of normotensive rats (-46.4+/-1.58 mV). Cirazoline did not produce a significant depolarisation in blood vessels of either normotensive or hypertensive rats. Perfusion with chloride-free solution resulted in a modest but significant hyperpolarisation (-8.0 mV) in the blood vessels of hypertensive but not in normotensive rats. 5. We conclude that salt-dependent hypertension in Dahl rats is accompanied by functional and biochemical changes in low-pressure blood vessels. These changes can, in part, be attributed to impairment in the basal, but not methacholine-stimulated, release of nitric oxide, and to altered chloride ion handling.

Topics: Adrenergic alpha-Agonists; Animals; Chlorides; Cyclic GMP; Endothelium, Vascular; Enzyme Inhibitors; Female; Hypertension; Imidazoles; Membrane Potentials; Methacholine Chloride; Myocytes, Smooth Muscle; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Nitroprusside; Propionates; Pulmonary Artery; Rats; Rats, Inbred Dahl; Receptors, Adrenergic, alpha; Sodium Chloride; Vasoconstriction

The effects of chloride-free buffer in the absence or presence of the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), or chloride channel antagonist, indanyloxyacetic acid 94 (IAA-94) on alpha(1)-adrenoceptor mediated contractions were investigated in aortic rings from Dahl salt-resistant normotensive (SRN) and salt-sensitive hypertensive (SSH) rats on a 4% salt diet.. Systolic and diastolic blood pressure were measured via intra-arterial catheters under halothane anesthesia. Subsequently, the aorta was removed and cirazoline-induced contractions were recorded in normal Krebs and chloride-free buffer using ring preparation. Guanosine 3',5'-cyclic monophosphate (cyclic GMP) content of aortic rings was also determined by scintillation proximity assay kits.. Systolic and diastolic blood pressure of SSH (180/130+/-1/1, mean+/-S.E.; n=14) were significantly higher than those of SRN (101/76+/-1/1, mean+/-S.E.; n=14) 7 weeks after they were placed on a salt diet. While the presence of L-NAME failed to have any impact on cirazoline-induced contractions in aortic rings from SSH rats, it significantly accentuated the effects of cirazoline in tissues from SRN rats. On the other hand, IAA-94 was able to inhibit cirazoline-mediated contractions in aortic rings from both SRN and SSH rats. The removal of chloride ions potentiated contractions produced by cirazoline in tissues from SRN but not SSH rats. Moreover, cirazoline-evoked responses in tissues from SRN were not further accentuated by the inclusion of L-NAME in chloride-free buffer. Cirazoline-mediated contractions in tissues from SSH rats were not influenced by absence of chloride ions, and the presence of L-NAME. It was also apparent that the inclusion of IAA-94 in absence of chloride ions did not prevent the potentiation of responses to cirazoline. Removal of chloride ions did not significantly decrease basal cyclic GMP levels in aortic rings from either strain.. Basal release of nitric oxide seems to make a greater contribution in the suppression of cirazoline-evoked contractions in vessels from SRN as opposed to SSH rats. Chloride channels appear to contribute to cirazoline-evoked contractions in normal Krebs but not in chloride-free buffer.

Topics: Adrenergic beta-Agonists; Analysis of Variance; Animals; Aorta; Chloride Channels; Chlorides; Cyclic GMP; Endothelium, Vascular; Enzyme Inhibitors; Female; Glycolates; Imidazoles; In Vitro Techniques; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Rats; Rats, Inbred Dahl; Vasoconstriction