Electrogenesis of increased norepinephrine sensitivity of arterial vascular muscle in hypertension.
The possibility that the vascular muscle cell might contribute to the development of essential hypertension by being more responsive to norepinephrine because of an inherently lower membrane potential (Em) was investigated. Experiments were designed to test the hypothesis that Em of arterial vascular muscle cells from spontaneously hypertensive rats (SHR) are less negative than those from matched Kyoto normotensive rats (KNR). The caudal artery, a muscular, densely innervated regulating artery 300-400 mum in outside diameter, which is activated by graded (nonspiking) depolarization to produce a maintained contraction, was studied. Vascular muscle cells from SHR always had less negative Em than those from KNR at 16 degrees C, but not at 36 degrees C, over a range of K+ concentrations from 2.7 mM to 150 mM. From the relationship between Em and K+ concentration, intracellular K+ concentration ([K+]i) was estimated to be 150 mM for SHR and 170 mM for KNR. The caudal artery undergoes a large depolarization when K+ is removed from the superfusing solution and a transient hyperpolarization that exceeds the calculated EK (potassium equilibrium potential) when K+ is replaced. The magnitude of the hyper-polarization on returning to 30 mM or 50 mM K+ always was greater for vascular muscle of SHR than KNR. The apparently lower [K+]i and more active (compensating) electrogenic ion transport in the SHR vascular muscle cells thus result in an unaltered Em at body temperature in the physiological range of K+ concentrations. However, depolarization by norepinephrine was greater over the middle of the dose-response curve, and this greater depolarization caused the contractions of SHR arteries to be greater. The altered electrogenesis of the SHR vascular muscle cells is postulated to provide a mechanism for the increased reactivity of arteries to norepinephrein in hypertension.
D000818:Animals; D001158:Arteries / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000209:etiology*; D007474:Ion Exchange; D008564:Membrane Potentials / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology; D051381:Rats; D013696:Temperature; D014655:Vascular Resistance
D011188:Potassium; D009638:Norepinephrine