Pharmacology & Therapeutics
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Item CATION CONTENT AND FLUXES IN RED CELLS OF NORMAL AND HYPERTENSIVE NIGERIANS(1978-08) ADEROUNMU, A. F.RED CELL SODIUM AND POTASSIUM CONTENT AND FLUXES IN NORMAL AND HYPERTENSIVE NIGERIANS. 1. Erythrocyte sodium, potassium and water content have been determined in 908 Nigerians so as to: 1. establish normal values in Nigerians 2. compare values in Nigerians with known values in other blacks. 3. compare values in Nigerians with those of caucasians. Red cell sodiuum, potassium and water were also determined in 7 caucasians who had been resident in Nigeria for periods varying from 6 months to 18 years. The RBC sodium for Nigerians considerably higher than those of caucasians, but the RBC potassium and water did not show any significant difference. In the course of this work, the normal (control) subjects were grouped according to their genotypes. 3 genotypes were encountered: AA, AS and AC. There was no significant difference in the erythrocyte sodium, potassium and water of the individuals belonging to these 3 genotypes. The results were also analysed for sex and age differences, and none was found. Results of erythrocyte sodium, potassium and water from 3 siblings and their mother were also presented. These results differed, from one another, suggesting that environmental factors are also important and probably just as potent determinants of RBC sodium, potassium and water content as are genetic factors. 2. 100 hypertensive subjects were studied. They were all newly diagnosed, mostly symptomless ambulant subjects who were attending the medical out-patient department of the University College Hospital, Ibadan. Their main pathological finding systemic hypertension. They were followed up for periods varying from 18 months to 3 1/2 years. Investigations were performed on each patient which enabled their being grouped into hypertensives with normal renal function or hypertensives with abnormal renal function. Only those with normal renal function were included in the study. The results obtained for the red cell sodium and potassium were significantly different from those of the Controls. Their red cell water was also significantly different from that of the Controls, but the difference m RBC water was not sufficient to account for the differences in the RBC sodium and potassium. Here again, the RBC sodium and potassium were not related to age or sex. The RBC sodium and potassium content were in no way related to the mean blood pressures. Their values remained the same both before and during treatment. Adequate control and maintenance of the patients blood pressures within the normal range did not affect these two cations. 3. When red cells from Controls and red cells from Hypertensives were exposed to a high sodium load, the RBCs from hypertensive gained a lot more sodium and lost a lot more potassium than the RBCs from Controls. 4. Normal red cells lost their potassium into isotonic sucrose media seven times as fast as red cells from hypertensive subjects. 5. Normal red cells have a slightly higher a tive sodium flux per hour than red cells from hypertensive subjects, but the difference is not statistically significant. The rate constant for active sodium flux is higher for red cells of Controls than for red cells of hypertensive subjects, but the correlation between intracellular sodium content and rate constant is not good (r= -0.43). The rate constant for the red cells of the hypertensives is lower, but it correlates better with the red cell sodium (r =0.53).Item INTERACTION OF PROSTAGLANDIN E(2) (PGE(2)) WITH NORADRENALINE AND ITS ANTAGONISTS IN THE ISOLATED MESENTERIC ARTERY OF RAT(1980-07) ADEAGBO, A. S. O.The effect of PGE(2), PGF(2a) and PGI(2) on constriction induced by different mechanisms was studied in the isolated rat mesenteric artery as described by McGregor (1965) Vasoconstriction was induced by mechanisms involving dif modes of calcium utilization viz: (i) Pharmacomechanical pathway by low doses of the adrenergic neurotransmitter, noradrenaline acting at α- receptor; (ii) electromechanical pathway by high potassium and (iii) agents which facilitate Ca(2t) influx e.g. A23187. The prostaglandins potentiated the vasoconstrictor effect of NA. Potentiation factors calculated from different doses of the prostaglandins showed the effects of the prostaglandins to be dose - dependent and PGE(2) to be significantly more potent (P>0.005) than PGF(2a) and PGI(2). The prostaglandins failed to potentiate high potassium - induced vasoconstriction. PGE(2) also failed to potentiate NA if the vasoconstrictor effects were evoked in Ca(2+) - free Krebs solution; but the degree of potentiation increased with increase in the concentration of Ca(2+) ions in the perfusion fluid. This result suggested strongly that the potentiation was associated with external calcium. Evidence is presented to show that potentiation was not prejunctional since cocaine, bretylium and reserpine pretreatment did not materially alter the effect of PGE(2). It was concluded that prostaglandins potentiated NA vasoconstriction by facilitating Ca(2a) influx. The mechanism of this facilitation is discussed. NA vasoconstriction was competitively antagonised by adrenoceptor antagonists-phentolamine, tolazoline, yohimbine and phenoxybenzamine (in low concentrations). The blockade caused by these antagonists was reversed by PGE(2). By comparing NA dose-ratios in the presence of antagonist with dose-ratios in the presence of antagonists plus different doses of PGB(2), I showed 1hat the degree of reversal was related to the dose of PGE. For example, the NA dose - ratio for yohimbine (1.28 x 10(-6)M) was reduced from 26.6 + 0.9 to 1.7 + 0.1 when PGE(2) (2.8 x 10(-8) M)was included in the perfusion fluid with the antagonist. The reverse of antagonism was not due to a change in the binding characteristics of the α- adrenoceptor since pA(2) values for the antagonist were not significantly different (P<0.05) when PGS was included with the antagonists. Evidence is presented which suggests that reversal of antagonism involved utilization of internally bound calcium since reversal of antagonism occured even after the omission of Ca(2+) from the external medium. In this sense, the mechanism of reversal was different from that of potentiation. Furthermore, the degree of reversal (measured as-reversal factor) was quantitatively greater than would be the case if reversal was simply a reflection of the enhgresponsiveness of the vascular muscle to NA. In contrast to the "competitive” α- adrenoceptor antagonists, PGE(2) did not reverse the block of NA vasoconstriction caused by phenoxybenzamine (high doses); verapamil, cinnarizine or prazosin. All these agents caused blockade of NA that was not competitive in nature. Since none of the competitive α- adrenoceptor antagonists prevent prostaglandin formation; the point is made, that a prostaglandin can reverse NA blockade even if the blockade did not involve inhibition of prostaglandin synthesis.