Central and peripheral effects of the peptide ANF on renal function and blood pressure in hypertensive rats.

Abstract

SUMMARY1. The present study assesses renal and blood pressure effects of systemically and intracerebroventricularly (I.c.v.) administered atrial natriuretic factor (ANF) in anaesthetized New Zealand genetically hypertensive (NZGH) rats and their normotensive substrain (NZN).2. Plasma ANF concentration was significantly raised in NZGH compared with NZN animals. Intravenous ANF administration increased circulating ANF concentration to similar levels in NZGH and NZN rats. Plasma aldosterone concentrations were initially similar in normotensive and hypertensive animals and were reduced markedly by i.v. ANF administration in both groups.3. Peripheral administration of ANF produced a significant and sustained hypotension during the period of the hormone administration in NZGH animals, while arterial mean blood pressure (MBP) was not altered significantly in NZN rats. Central infusion of ANF produced no change in MBP in either NZGH or NZN animals. There was no detectable change in heart rate during central or peripheral administration of the hormone in either group.4. By comparison with animals maintained on hormone-free infusate, urine flow changed little over the 80 min period of i.v. ANF infusion in NZGH r"t,s but was markedly increased in NZN animals. Urinary sodium excretion was elei .-ted during ANF infusion in both NZGH and NZN animals. Central infusion of Al F produced a diuresis in NZN rats but a slight reduction in urine flow in NZGH animals, while sodium excretion was not affected in either group. 5. It appears from the present study that central and peripheral ANF effects on renal function and blood pressure differ in hypertensive and normotensive animals. These differences may in part reflect adjustments to long-term elevation in plasma ANF in hypertension and in part are possibly associated with disturbances in related endocrine mechanisms.

Renal, endocrine and vascular effects of atrial natriuretic peptide in a novel vasopressin‐deficient genetically hypertensive strain of rat

“…This is in agreement with previous reports in hypertensive man (Tunny & Gordon, 1985;limura, Shimamoto, Ando, Ura, Ishida, Nakagawa, Yokoyamata, Fukuyama, Yamaguchi & Yamaji, 1987) and in other forms of hypertensive rats (Morii, Nakao, Kihara, Sugawara, Sakamoto, Yamori & Imura, 1986;Gutkowska, Kuchel, Racz, Buu, Cantin & Genest, 1986;Al-Barazanji & Balment, 1989). Although much higher plasma ANP levels were reported in vasopressin-replete New Zealand genetically hypertensive (1 18.3 + 4 fmol/ml) and normotensive (97.8 + 3 9 fmol/ml) animals subjected to the same experimental protocol (Al-Barazanji & Balment, 1989), the underlying relationship between elevated blood pressure and elevated ANP levels in these genetically hypertensive animals was not altered in the absence of the endogenous vasopressin. Our recent studies in the Brattleboro rats indicate that the influence of vasopressin on plasma ANP is perhaps more closely related to the resultant fluid balance than any specific action of vasopressin directly on ANP secretion (Burgess & Balment, 1992).…”

“…This decline in plasma aldosterone is in agreement with previous observations in the vasopressin-replete NZGH and NZN rats treated with ANP (Al-Barazanji & Balment, 1989). Similar effects have been reported in experimental hypertension (Volpe, Odell, Kleinert, Muller, Camargo, Laragh, Maack, Vaughan & Atlas, 1985).…”

“…Previously we reported that ANP administrationi in vasopressin-replete animals at the dose employed here reduced mean arterial blood pressure in NZGH rats only and not in NZN control animals (Al-Barazanji & Balment, 1989). In the present study ANP infusion produced a marked hypotensive effect in both DI/H and DI/N rats, though this was more pronounced in the former.…”

“…These animals permit the study of cardiovascular and renal function sensitivity to ANP in hypertension in the absence of the potential confounding influence of vasopressin. Accordingly, we can reassess the apparent hypersensitivity of the NZGH rat to the actions of ANP (Al-Barazanji & Balment, 1989), and examine the extent to which this may rely on the associated disturbance in AVP secretion in these animals (Ashton & Balment, 1989). The present investigation was undertaken to determine plasma ANP concentration in this novel AVP-deficient genetically hypertensive (DI/H) rat and its normotensive substrain (DI/N), and to examine the effects of rat ANP on arterial blood pressure and renal handling of water and sodium together with concomitant changes in other renally active hormones.…”

“…These animals permit the study of cardiovascular and renal function sensitivity to ANP in hypertension in the absence of the potential confounding influence of vasopressin. Accordingly, we can reassess the apparent hypersensitivity of the NZGH rat to the actions of ANP (Al-Barazanji & Balment, 1989), and examine the extent to which this may rely on the associated disturbance in AVP secretion in these animals (Ashton & Balment, 1989 Associates, Harrow, UK). The extraction efficiency for ANP was 83 + 1 8 % (n = 6), and the intra-assay coefficient of variation was 7 1 % (n = 9).…”