Effects of Endogenous Nitric Oxide Synthesis Inhibition on the Depressor Response to Intracerebroventricular Calcium

BACKGROUND: Aside from its well known peripheral antihypertensive effects, calcium also lowers blood pressure, when administered into the cerebral ventricle. The present study was aimed to determine whether the central depressor response to calcium is mediated by a stimulation of endogenous L-arginine-nitric oxide (NO) pathway. METHODA: Mean arterial pressure (MAP) and heart rate (HR) were continuously recorded from the femoral artery in anesthetized rats. Administration of calcium was performed into the right lateral cerebral ventricle. The effects of N G-nitro-L-arginine methyl ester (L-NAME) on the cardiovascular response to calcium were examined. RESULTS: Intracerebroventricular (ICV) injection of calcium consistently produced a decrease in MAP and HR. The depressor and bradycardiac responses to calcium showed a dose-dependent fashion. Pretreatment with a calcium channel blocker, diltiazem (1 micromol, ICV), attenuated cardiovascular responses to calcium. ICV infusion (1 microl/min) of L-NAME (200 microgram/kg and 20 microgram/kg/min for 60 min) increased MAP without significant changes in HR. Chronic ingestion of L-NAME (5 mg/100 ml in drinking water, 4 weeks) also increased the systolic blood pressure as compared with control. The depressor effect of ICV calcium was significantly diminished in acute or chronic L-NAME treated rats. CONCLUSION: These findings suggest that the central depressor response to calcium, at least in part, is NO-dependent.

Altered Vascular Response to the K+induced Vasorelaxation in Aortic Smooth Muscle of Renal Hypertensive Rats

BACKGROUND: An increase of the extracellular K+concentrations up to about 8 mM in the isolated vessels causes relaxation in pre-contracted state. In order to elucidate the mechanisms of K+induced relaxation and compare with that of 2-kidney, 1 clip (2K1C) renal hypertensive rats, we recorded aortic vascular tension using an organ bath study. METHOD: 2K1C hypertension was made by clipping the left renal artery and age-matched control rats received a sham treatment. Thoracic aortic rings were mounted in tissue baths for measurement of isometric contractile force. RESULTS: Exposure to K+(from 2 to 8 mM) relaxed a phenylephrine (2 x 10-6 M)-induced contraction in K+free Krebs-Ringer solution, dose-dependently. Ouabain (10-5 M) enhanced the K+induced relaxation in above 2 mM K+ The K+induced relaxation was still induced in endothelium-denuded condition. Incubation with the K+channel blockers such as tetraethylammonium (TEA, 1 mM), glibenclamide (10-5 M), 4-aminopyridine (3 mM), barium (5 mM) and cesium (2 mM) did not affect on the K+induced relaxation. In renal hypertensive rats, the K+induced relaxation was markedly suppressed and ouabain enhanced it. CONCLUSIONS: These results suggest that the K+induced relaxation in aorta be mediated by Na-pump independent mechanisms, and the decrease of the K+induced relaxation in the renal hypertensive rats may be a possible mechanism of hypertension.

Altered Vascular Response to the K+induced Vasorelaxation in Aortic Smooth Muscle of Renal Hypertensive Rats

BACKGROUND: An increase of the extracellular K+concentrations up to about 8 mM in the isolated vessels causes relaxation in pre-contracted state. In order to elucidate the mechanisms of K+induced relaxation and compare with that of 2-kidney, 1 clip (2K1C) renal hypertensive rats, we recorded aortic vascular tension using an organ bath study. METHOD: 2K1C hypertension was made by clipping the left renal artery and age-matched control rats received a sham treatment. Thoracic aortic rings were mounted in tissue baths for measurement of isometric contractile force. RESULTS: Exposure to K+(from 2 to 8 mM) relaxed a phenylephrine (2 x 10-6 M)-induced contraction in K+free Krebs-Ringer solution, dose-dependently. Ouabain (10-5 M) enhanced the K+induced relaxation in above 2 mM K+ The K+induced relaxation was still induced in endothelium-denuded condition. Incubation with the K+channel blockers such as tetraethylammonium (TEA, 1 mM), glibenclamide (10-5 M), 4-aminopyridine (3 mM), barium (5 mM) and cesium (2 mM) did not affect on the K+induced relaxation. In renal hypertensive rats, the K+induced relaxation was markedly suppressed and ouabain enhanced it. CONCLUSIONS: These results suggest that the K+induced relaxation in aorta be mediated by Na-pump independent mechanisms, and the decrease of the K+induced relaxation in the renal hypertensive rats may be a possible mechanism of hypertension.

Role of Tyrosine Kinases in 5-HT-Induced Vascular Contraction in Two-Kidney, One Clip Hypertensive Rats / 대한신장학회잡지

Tyrosine kinases have been implicated in vascular smooth muscle cell proliferation and contraction. The involvement of tyrosine kinases in 5-hydroxytryptamine (5-HT)-induced contractile response of the isolated aorta was examined in two-kidney, one clip (2K1C) hypertensive rats, 2141C hypertension was made by constricting the left renal artery and age-matched control rat received sham treatment. Thoracic aortic rings denuded of endotheliurn were mounted in tissue bath, for measurement of isometric contractile force. The putative tyrosine kinase inhibitor, genistein, shifted concentration-response curves to 5-HT toward the right in control rats The isometric force generation induced by 5-HT was also inhibited by genistein in aortic rings from 2K1C: hypertensivc rats, however genistein did not affect on the high concentration of 5-HT in hypertensive rat ;. Genistein-induced relaxations were more attenuated in aortae from hypertensive rats than those from control Genistein had no effect on contrartcion elicited by the direct protein kinase C activator, phorbol 12, 13 dibutyrate (PDBu) either in 2KlC hypertensive or in control Group. These findings indicate that genistein-sensitive tyrosine kinases paeticipate in 5-HT-induced contraction of rat aortic smooth muscle, of which role is apparent in 2K1C: hypertension.

Pressor Responses to Intracerebroventricular Infusion of Hypertonic NaCl in Renal Hypertensive Rats

BACKGROUND: The sodium concentration in the central nervous system may play an important role in cardiovascular function and body fluid regulation. The purpose of this investigation was to examine the effects of intracerebroventricular (ICV) infusion of hypertonic NaCl solutions on the cardiovascular responses in normotensive and 2-kidney, 1 clip (2K1C) renal hypertensive rats. METHODS: 2K1C hypertension was made by clipping the left renal artery and were used 4 weeks later. Age-matched control rats received a sham treatment. Under thiopental (50 mg/kg, IP) anesthesia, both isotonic and hypertonic NaCl solutions (0.15 M, 0.6 M and 1.2 M) were ICV applied, while blood pressure and heart rate (HR) responses were continuously monitored. RESULTS: Central administration of hypertonic NaCl solution caused an elevation in mean arterial pressure (MAP) and HR in both normotensive and 2K1C hypertensive rats. The response magnitude in the blood pressure was positively correlated to the NaCl concentration in normotensive rats, while the pressor responses to hypertonic NaCl were comparable regardless of the concentration of NaCl in hypertensive rats. Despite of the HR responses were similar in between two groups, the magnitude of the MAP increases were more elevated in hypertensive than in normotensive control rats. Isotonic NaCl solution, when centrally applied, caused an elevation in blood pressure only in hypertensive rats. CONCLUSION: These results indicate that the central sensitivity to sodium chloride is altered in 2K1C renal hypertensive rats.

Cardiovascular Effects of Nifedipine and Bay K 8644 in Hypertensive Rats

BACKGROUND: Calcium plays a key role in vascular contraction and regulates receptor sensitivity to certain neurotransmitters. Calcium channel blockers are useful in the treatment of both clinical and experimental hypertension. The present study was designed to examine whether there is an alteration of the activity of calcium channels in association with the development of hypertension. METHODS: Deoxycorticosterone acetate(DOCA)-salt hypertension was made by subcutaneous implantation of DOCA(200mg/kg)strip plus saline drinking(1%) and 2-kidney, 1 clip(2KIC)hypertension by clipping the left renal artery with a silver clip(internal gap of 0.2mm). They were used 4 weeks later. Age-matched normal rats served as a control. Mean arterial pressure(MAP) and heart rate(HR) were continuously recorded from the right femoral artery. The drugs were administered intravenously. RESULTS: Vehicle alone was without effect on MAP or HR. In normotensive rats, nifedipine infusion(5 and 10ug/kg/min)caused a dose-dependent decrease in MAP without significant changes in HR, while Bay k 8644(Bay K, 5 and 10 ug/kg/min) increased MAP transiently. Both the depressor response to nifedipine and the pressor response to Bay k were more marked in DOCA-salt hypetensive rats than in normotensive rats. The maximal changes in MAP indced by nifedipine(5 and 50 ug/kg) or Bay K(5 and 50 ug/kg) were also enhanced in 2KIC hypertensive rats as compared with control rats. CONCLUSION: These results indicate that calcium channel inhibitors and activators can affect on the regulation of blood pressure in an opposite fashion. It is also suggested that the activity of calcium channels might be altered in the developement of experimental hypertension.