Studies on Experimental Hypertension in the Rat and Cat

Abstract

A study has been made of mechanisms involved in the production and maintenance of experimentally induced hypertension in the rat and cat. An indirect tail cuff method for the determination of rat blood pressures was developed and provided accurate values for the systolic blood pressure. An improved method for measuring the blood pressure of conscious, unrestrained cats was also developed. Hypertension was produced consistently in the rat and cat by using either a DOCA-NaC1 regimen or the method of Grollman. The pathologies of these hypertensions were found to be similar in both species. No clear explanation for the rapid production of DOCA-NaC1 hypertension in rats, which occurred in these laboratories, was found although the strain, age, and housing of the rats were considered to be possibly implicated. The involvement of the sympathetic nervous system in the production of DOCA-NaC1 hypertension in rats was revealed in a study involving the inhibition of peripheral sympathetic nerves with guanethidine. Whilst a potent adrenergic neuronal blockade was present, the rise in blood pressure produced by a DOCA-NaC1 regimen was prevented. In a similar series of experiments, a lack of dependency on the sympathetic nervous system for the production of one-kidney renal hypertension was shown. Cardiovascular reactivity in both DOCA-NaC1 hypertensive rats and renal hypertensive cats revealed a lack of true hypersensitivity of vascular smooth muscle to pressor agents. The involvement of the renin-angiotensin system in the production of renal hypertension and the sympathetic nervous system in the maintenance of both DOCA-NaC1 and renal hypertensions was also revealed. The antihypertensive effect of both guanethidine and α-methyldopa in DOCA-NaC1 hypertensive rats and renal hypertensive cats also provided evidence for the importance of the sympathetic nervous system. The mechanism of action of α-methyldopa was shown to be due to a central action of its metabolite, α-methylnoradrenaline.