sq-23377 and Cerebrovascular-Disorders

Mesangial cells (MC) are considered to play an important role in the development of hypertension. The purpose of this study was to characterize the effects of cytosolic Ca2+ on membrane voltage and conductance of MC using stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY). We applied the patch-clamp technique in the whole-cell configuration to measure membrane potential (Vm) and ion currents. There was no significant difference in resting Vm values between MC from WKY and SHRSP. The cytosolic Ca2+ increase induced membrane depolarization and the increase of Cl- currents in MC from WKY but not in MC from SHRSP. On the other hand, the Ca2+ increase induced membrane hyperpolarization and the increase of K+ currents in MC from SHRSP but not in MC from WKY. Such differences between MC from two rat strains may play an important role in the alterations in renal hemodynamics observed in hypertension.

Topics: Animals; Calcium; Cells, Cultured; Cerebrovascular Disorders; Chloride Channels; Disease Models, Animal; Electric Conductivity; Glomerular Mesangium; Hypertension; Ionomycin; Membrane Potentials; Patch-Clamp Techniques; Potassium Channels; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Time Factors

We have reported that cytosolic Ca2+ concentration ([Ca2+]i) is increased in platelets from spontaneously hypertensive rats (SHR) in both basal and thrombin-stimulated conditions. To determine whether the correlation between blood pressure and cellular Ca2+ metabolism exists in stroke-prone SHR (SHRSP), we investigated Ca2+ handling using fura 2 and aggregation response in platelets of 12- to 13-week-old male SHRSP, SHR, and Wistar-Kyoto rats (WKY). Systolic pressure was highest in SHRSP and lowest in WKY (213 +/- 8, 172 +/- 7, and 135 +/- 5 mm Hg, respectively). Basal [Ca2+]i was significantly higher in SHR than WKY (45.9 +/- 4.5 versus 41.2 +/- 4.8 nmol/L, P<.05), and that in SHRSP (40.2 +/- 2.8 nmol/L) was similar to that in WKY. Thrombin (0.1 IU/mL)-stimulated [Ca2+]i rise was greater in SHR and smaller in SHRSP than in WKY in the presence of extracellular Ca2+ (530 +/- 50 and 408 +/- 52 versus 475 +/- 50 nmol/L, respectively; P<.05). The recovery rate from the peak [Ca2+]i response to thrombin was greatest in SHRSP and least in WKY. Ionomycin (5 micromol/L)-stimulated [Ca2+]i rise was similar in WKY, SHR, and SHRSP (731 +/- 97, 743 +/- 88, and 683 +/- 70 nmol/L, respectively). Thrombin-induced maximum platelet aggregation response was higher in SHR and lower in SHRSP than WKY (82 +/- 4 percent and 61 +/- 15 percent versus 73 +/- 6 percent, respectively; P<.05). In contrast to SHR, basal [Ca2+]i in SHRSP was similar to that in WKY, and thrombin-stimulated [Ca2+]i was attenuated. These result suggest that platelet Ca2+ handling differs between SHR substrains and that an increased [Ca2+]i is not obligatory in genetically hypertensive rats.

Topics: Animals; Blood Platelets; Blood Pressure; Calcium; Cerebrovascular Disorders; Cytosol; Fura-2; Hypertension; Ionomycin; Male; Platelet Aggregation; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Thrombin

In previous studies, we measured a greater intracellular free calcium concentration and net potassium efflux, possibly calcium activated, in lymphocytes from spontaneously hypertensive stroke-prone rats (SHRSP) as compared with Wistar-Kyoto (WKY) rats. In this study, we addressed two related questions: 1) Can the greater intralymphocytic calcium concentration of the SHRSP account for the greater net potassium efflux? 2) Is the calcium sensitivity of calcium-activated potassium channels in lymphocytes from SHRSP different as compared with that of those from WKY rats? Ionomycin, a calcium ionophore, caused a concentration-dependent and proportional increase in net potassium efflux and intracellular free calcium concentration in lymphocytes from both strains of rat. Based on the relations between net potassium efflux and intracellular free calcium concentration established with ionomycin, the resting net potassium efflux of lymphocytes from SHRSP is greater than would be predicted based on the resting intracellular free calcium concentration. Using the patch clamp technique, we were able to identify and characterize a calcium-activated potassium channel in the plasma membrane of lymphocytes from both strains of rat. Potassium currents were recorded that had a slope conductance of 18.1 +/- 1.49, n = 6, and 18.5 +/- 1.44, n = 7, in WKY rat and SHRSP thymocytes, respectively. The channel exhibited rectification of the outward current in both strains of rat. Channels tended to appear in clusters of two or more per patch and were recorded in 30-50% of the patches examined. Calcium sensitivity of the channels was similar; maximum activation occurred at 700 nM free calcium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Calcium; Cerebrovascular Disorders; Disease Susceptibility; Drug Resistance; Electric Conductivity; Female; Ionomycin; Lymphocytes; Male; Potassium Channels; Rats; Rats, Inbred SHR; Rats, Inbred WKY