ABSTRACT
Multiple cell membrane alterations have been reported to be the cause of various forms of hypertension. The present study focuses on the lipid portion of the membranes, characterizing the microviscosity of membranes reconstituted with lipids extracted from the aorta and mesenteric arteries of spontaneously hypertensive (SHR) and normotensive control rat strains (WKY and NWR). Membrane-incorporated phospholipid spin labels were used to monitor the bilayer structure at different depths. The packing of lipids extracted from both aorta and mesenteric arteries of normotensive and hypertensive rats was similar. Lipid extract analysis showed similar phospholipid composition for all membranes. However, cholesterol content was lower in SHR arteries than in normotensive animal arteries. These findings contrast with the fact that the SHR aorta is hyporeactive while the SHR mesenteric artery is hyperreactive to vasopressor agents when compared to the vessels of normotensive animal strains. Hence, factors other than microviscosity of bulk lipids contribute to the vascular smooth muscle reactivity and hypertension of SHR. The excess cholesterol in the arteries of normotensive animal strains apparently is not dissolved in bulk lipids and is not directly related to vascular reactivity since it is present in both the aorta and mesenteric arteries. The lower cholesterol concentrations in SHR arteries may in fact result from metabolic differences due to the hypertensive state or to genes that co-segregate with those that determine hypertension during the process of strain selection.
Subject(s)
Animals , Male , Rats , Aorta/chemistry , Cell Membrane/chemistry , Cholesterol/analysis , Hypertension/metabolism , Mesenteric Arteries/chemistry , Phospholipids/analysis , Cholesterol/chemistry , Electron Spin Resonance Spectroscopy , Gas Chromatography-Mass Spectrometry , Hypertension/etiology , Muscle, Smooth, Vascular/chemistry , Muscle, Smooth, Vascular/cytology , Phospholipids/chemistry , Rats, Inbred SHR , Rats, Inbred WKYABSTRACT
Hypertension is one of the major precursors of atherosclerotic vascular disease, and vascular smooth muscle abnormal cell replication is a key feature of plaque formation. The present study was conducted to examine the relationship between hypertension and smooth muscle cell proliferation after balloon injury and to correlate neointima formation with resting membrane potential of uninjured smooth muscle cells, since it has been suggested that altered vascular function in hypertension may be related to the resetting of the resting membrane potential in spontaneously hypertensive rats (SHR). Neointima formation was induced by balloon injury to the carotid arteries of SHR and renovascular hypertensive rats (1K-1C), as well as in their normotensive controls, i.e., Wistar Kyoto (WKY) and normal Wistar (NWR) rats. After 14 days the animals were killed and the carotid arteries were submitted to histomorphometric and immunohistochemical analyses. Resting membrane potential measurements showed that uninjured carotid arteries from SHR smooth muscle cells were significantly depolarized (-46.5 + or - 1.9 mV) compared to NWR (-69 + or - 1.4 mV), NWR 1K-1C (-60.8 + or - 1.6 mV), WKY (-67.1 + or - 3.2 mV) and WKY 1K-1C (-56.9 + or - 1.2 mV). The SHR arteries responded to balloon injury with an enhanced neointima formation (neo/media = 3.97 + or - 0.86) when compared to arteries of all the other groups (NWR 0.93 + or - 0.65, NWR 1K-1C 1.24 + or - 0.45, WKY 1.22 + or - 0.32, WKY 1K-1C 1.15 + or - 0.74). Our results indicate that the increased fibroproliferative response observed in SHR is not related to the hypertensive state but could be associated with the resetting of the carotid smooth muscle cell resting membrane potential to a more depolarized state
Subject(s)
Animals , Rats , Angioplasty, Balloon/adverse effects , Carotid Artery Injuries/pathology , Hypertension, Renovascular/complications , Muscle, Smooth, Vascular/pathology , Analysis of Variance , Carotid Artery Injuries/etiology , Case-Control Studies , Cell Count , Disease Models, Animal , Membrane Potentials , Rats, Inbred WKY , Rats, Wistar , Tunica Intima/pathologyABSTRACT
The increase in sensitivity of guinea pig preparations to bradykinin (BK) due to stretching occurring with time after mounting was studied by determining the time course of changes in the cell membrane potential, measured with intracellular microelectrodes. A sustained hyperpolarizing effect of BK, which was observed in recently mounted preparations, became transient after 120 min, when it was followed by depolarization, which was much more evident after 4 h of stretching. As a consequence, a parallel increase in the contractile response to BK was also observed. The hyperpolarizing effect was due to the opening of Ca²+-dependent K+ channels sensitive to apamin, since BK dose-response curves done within 1 h of mouting were shifted to the left, becoming similar to dose-response curves obtained 4 h after mounting of the guinea pig ileum preparation. These results were specific for BK, since the potentiating effect of apaming was not observed for acetylcholine. Our results show that the activation of B2 receptors by BK in the isolated guinea pig ileum induce a dual effect - hyperpolarization and depolarization - and that the increase in the contractile response consequent to stretching is probably due to the inactivation of apaminsensitive Ca²+-dependent K+ channels
Subject(s)
Guinea Pigs , Animals , Muscle Contraction/physiology , Muscle, Smooth/physiology , Receptors, Bradykinin/physiology , Apamin/pharmacology , Bradykinin/pharmacology , Calcium Channels , Calcium Channels/physiology , Potassium Channels , Potassium Channels/physiology , Muscle Contraction , Membrane Potentials/drug effects , Membrane Potentials/physiology , Muscle Relaxation/drug effects , Muscle Relaxation/physiology , Muscle, Smooth , Receptors, Bradykinin/drug effectsABSTRACT
The response of the rat duodenum to bradykinin (BK) consists of relaxant and contractile components, which have been atributed to different receptor types. To characterize the receptor responsible for this diphasic response we studied the effects of BK analogues known to act on B1 or B2 receptors in other systems. DesArg**9-Leu**8-BK and Thi**5,**8DPhe**7-BK presented only relaxant and only contractile effects, respectively, whereas DArgOHyp883Thi**5,**8DPhe**7-BK was a potent antagonist of the relaxation (but not of the contraction) induced by BK. Our results show that the relaxant and contractile components of the rat duodenum's response to BK are due to B2 and B1 receptor subtypes, respectively
Subject(s)
Rats , Animals , Female , Bradykinin/pharmacology , Duodenum/metabolism , Receptors, Neurotransmitter/metabolism , Amino Acid Sequence , Bradykinin/analogs & derivatives , Bradykinin/metabolism , Muscle Contraction , Muscle Relaxation/drug effectsABSTRACT
The development of tachyphylaxis to [1-sarcosine]-angiotensin II was studied in helical strips and everted rings of rabbit aorta. Strips, but not everted rings, developed marked (>50%) tachyphylaxis to the peptide, when challenged repeatedly at 1-h intervals. Measurements of the membrane potential showed no difference between the two preparations, but strips were more sensitive to KC1 than everted rings. These results suggest that the strips are more depolarized than the everted rings due to lesions caused by the spiral cutting. This partial depolarization may underlie the tachyphylactic phenomenon