Parathyroidectomy, cardiovascular reactivity and calcium distribution in aorta and heart of spontaneously hypertensive rats

In order to elucidate the mechanisms by which parathyroidectomy (PTX), performed in young spontaneously hypertensive rats (SHR), delays the development and attenuates the level of hypertension, we studied, in vivo, cardiovascular reactivity (CVR, blood pressure response to bolus noradrenaline administration), aortic calcium distribution and cardiac calcium content in SHR with or without parathyroid glands. PTX was performed in 6-week-old animals and experiments were done in pretreated anaesthetized animals 2 and 22 weeks after surgery. A significantly decreased CVR was observed 22 weeks after PTX in SHR-PTX as compared with controls. These data are not specific for hypertensive animals since similar data are also obtained on normotensive Wistar rats treated in an identical fashion. In addition, after PTX in SHR and Wistar rats myocardial (auricle and ventricle) calcium content was more rapidly reduced (after 2 weeks) than aortic membrane-bound and cellular calcium fractions. The present studies established that PTX decreased CVR and alters calcium content and distribution in the cardiovascular systems of rats from hypertensive and normotensive strains. Furthermore, the results confirm a requirement for the parathyroid glands in the pathogenesis of spontaneous hypertension in SHR and for the normal CVR.     

Heparin lowers blood pressure and vascular calcium uptake in hypertensive rats

Increased calcium uptake by vascular tissue, leading to elevated cytosolic calcium, has been implicated in the pathophysiology of hypertension. Heparin treatment of hypertensive rats has been known to lower blood pressure but its mechanism is not known. This study examined the effect of chronic heparin treatment on systolic blood pressure, aortic calcium and 87Rubidium (86Rb) uptake of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Starting at 12 weeks of age SHR and WKY rats were given either sodium heparin 300 units s.c. or equal amounts of saline once a day for a period of 6 weeks. At 18 weeks, systolic blood pressure, uptakes of calcium and 86Rb by aortae were significantly higher (p less than 0.01) in saline-treated SHR compared with heparin-treated SHR and WKY. Heparin treatment lowered the elevated calcium and 86Rb Uptake and blood pressure in SHR but had no effect on WKY. The parallel increase in systolic blood pressure and vascular calcium uptake suggests that increased calcium uptake mechanisms are associated with hypertension in SHR. Heparin appears to lower elevated blood pressure in SHR by lowering elevated vascular calcium uptake.     

Effect of renovascular hypertension on experimental glomerulonephritis in rats.

Systemic hypertension is a major risk factor that determines the rate of progression of kidney disease. The underlying mechanisms, however, are incompletely understood. To gain insight into these mechanisms, the present study was undertaken to characterize the effects of renovascular hypertension on the course of anti-thymocyte antibody-induced glomerulonephritis. Glomerulonephritis was induced in rats 6 weeks after the initiation of two-kidney, one-clip hypertension, when blood pressure was already increased. Structure and function of the clipped and the nonclipped kidney were examined 5 days later. Glomerular filtration rate (GFR) was measured by inulin clearance. The induction of nephritis did not alter the blood pressure in either hypertensive rats or normotensive controls. Albuminuria increased slightly in normotensive rats after the induction of nephritis, whereas no significant differences were found between hypertensive rats with or without nephritis. No significant differences were found for the GFR values of normotensive controls and nephritic animals or for values in the clipped kidney with or without nephritis. However, the GFR of the nonclipped kidney was significantly reduced in nephritic animals as compared with all other groups. Morphologic evaluation revealed that hypertensive rats with nephritis exhibited a combination of characteristics of nephritis and hypertensive glomerular injury. Histologic findings of nephritis, such as glomerular binding of rabbit IgG and glomerular proliferation and mesangial matrix expansion, were similar after the induction of nephritis in controls and in the clipped and nonclipped kidneys of hypertensive animals. However, intraglomerular microaneurysms were significantly more often found in the non-clipped kidneys after the induction of nephritis. Hypertension-induced deterioration of glomerular function was not associated with marked morphologic deterioration but rather with a combination of the characteristics of nephritis and hypertensive glomerular injury.     

Altered element concentrations in tissues of spontaneously hypertensive rats

The involvement of elements in the pathological process of primary hypertension has been established. The tissue distribution of 12 elements was studied in spontaneously hypertensive rats (SHR) and normotensive homologous rats (WKY). A multi-element analytical technique allowed simultaneous determination of sodium, potassium, calcium, magnesium, strontium, rubidium, manganese, copper, zinc, iron, sulphur and phosphorus in blood, plasma, brain, liver, kidney, skeletal muscle, heart and bone. Most elements were modified in SHR, except Ca, Rb and S. In plasma, an increase in Cu (+22%) and a decrease in K (-8%), Mg (-15%) and P (-11%) were observed. These variations, qualitatively similar to those found in man, suggest that the results in animal tissues could be extrapolated to man. Modifications were observed in all the tissues tested. Among them significant variations were noted in Na (+18%), Mn (+12%) and Cu (+29%) in kidney, and in K (+5%), Mg (+9%), Sr (-29%) and Zn (+14%) in heart. The role of these plasma and tissue variations in hypertension is discussed, as well as the possible involvement of the hypertensive process and/or hormones.     

EFFECTS OF CALCIUM ENTRY BLOCKERS ON BLOOD PRESSURE AND HEART RATE IN NEUROGENIC HYPERTENSIVE DOGS

The hypotensive and negative chronotropic effects of 5 calcium entry blockers (verapamil 200 micrograms/kg IV; diltiazem 300 micrograms/kg IV; nifedipine 5 micrograms/kg IV; nicardipine 50 micrograms/kg IV; and bepridil 5 mg/kg IV) were compared in control normotensive and acute neurogenic hypertensive anaesthetized dogs. Acute neurogenic hypertension was induced by sino-aortic denervation (SAD). In control normotensive dogs, all drugs (except bepridil) induced a slight and transient decrease in blood pressure. Nifedipine and nicardipine increased heart rate whereas the three other drugs remained ineffective. SAD caused a 2-2.5-fold increase in the hypotensive properties of the 5 drugs in dogs. Moreover, the duration of this induced hypotension was longer than in control normotensive animals. In SAD dogs, all calcium entry blockers significantly decreased heart rate. This study indicates that the direct cardiac inhibitory action of calcium channel blockers is modulated by baroreceptor activity in intact animals. The mechanism of the selective action of calcium entry blockers in hypertensive SAD in contrast to normotensive dogs is discussed.     

Effect of antitonin on blood pressure in the one-kidney hypertensive rat.

1. The tonin concentration of saliva and submaxillary glands was studied in one-clip hypertensive rats with or without the contralateral kidney. 2. Salivary tonin concentration was elevated in one-kidney hypertensive rats, but not in one-kidney normotensive or two-kidney, one-clip hypertensive rats. In contrast, an elevated submaxillary gland tonin concentration was found only in uninephrectomized animals, whether normotensive or hypertensive. 3. A single intravenous administration of rabbit tonin antiserum into one-kidney hypertensive rats restored blood pressure to normal in seven out of ten animals. There was little change in blood pressure in two-kidney, one-clip hypertensive, uninephrectomized or sham-operated rats. 4. These findings suggest a connection between the physiology of the kidney and of the submaxillary gland in the rat, and indicate that tonin may play a significant role in maintaining high blood pressure in one-kidney hypertensive aniamls.     

Cytoplasmic free [Ca2+] is increased in the platelets of spontaneously hypertensive rats and essential hypertensive patients

The cytoplasmic free calcium concentration [( Ca2+]i) was assessed with the fluorescent dye Quin 2 in platelets and lymphocytes of spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), essential hypertensive patients (EHP) and normotensive human control subjects (NCS). [Ca2+]i was significantly higher in the platelets of 8- and 20-week-old SHR in comparison with WKY. However, no difference was evident after weaning. Changes of cellular calcium in hypertensive rats apparently evolved simultaneously with the development of high arterial pressure. [Ca2+]i was significantly higher in platelets of EHP than in NCS. In lymphocytes of SHR, [Ca2+]i was not different from WKY at 4 and 8 weeks, but was increased at 14 weeks and at older ages. In EHP, intralymphocytic [Ca2+] was only modestly higher than in controls. On the whole, the results suggest that control of cytoplasmic calcium in these blood cells is similarly affected in human and animal models of primary hypertension.     

Calmodulin reduces ouabain-sensitive ATPase of cardiac sarcolemmal membranes: high reduction in spontaneously hypertensive rats

Calmodulin and calcium effects on cardiac ouabain-sensitive adenosine triphosphatase (ATPase) activity were studied in young spontaneously hypertensive rats (SHR) and in their normotensive control Wistar-Kyoto rats (WKY). Cardiac sarcolemmal membranes from SHR showed significantly higher ouabain-sensitive ATPase activity than membranes from WKY rats. This activity was unaffected by calmodulin or calcium alone. However, when both calmodulin and calcium were added, ouabain-sensitive activity was significantly reduced without changes in the total ATPase activity. The calcium-dependent calmodulin effect was dose-dependent and greater in SHR than in WKY membranes. An altered interaction between the calcium-calmodulin system and sodium handling by the plasma membrane in SHR may play a role in the pathogenesis of hypertension.     

Time course of changes in the norepinephrine content of tissues from spontaneously hypertensive and Wistar Kyoto rats

The change in norepinephrine (NE) content with age (from 2 days to 17 weeks old) was examined in a variety of tissues from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats. NE content was determined by either a catechol-O-methyltransferase-based radioenzymatic assay or high performance liquid chromatography with electrochemical detection. Regardless of the age of the animal, NE content per gram of tissue was significantly greater in mesenteric arteries and kidneys from SHR compared to WKY tissues, whereas NE content per whole kidney was similar between the two rat strains. The time course of enhanced NE content in caudal arteries and aortas from SHR followed the development of hypertension. In the spleen, NE content per gram of tissue was elevated in young SHR; however, in adult rats NE content was not significantly different between the two rat strains. Because spleens from WKY rats were substantially larger, total NE content per spleen was significantly greater in tissues from WKY rats. Cardiac contents of NE were similar in SHR and WKY rats at all ages examined. Adrenal epinephrine concentrations were similar in SHR and WKY rats, whereas NE content was elevated in the SHR at 46 and 81 days of age. The results of the present study demonstrate that the appearance of increased NE levels in some SHR tissues occurs before the development of hypertension in this model. If NE content is a valid index of sympathetic innervation, enhanced innervation may contribute to the vascular medial hypertrophy observed in young SHR and the elevation of blood pressure in these rats.     

Role of the D1A dopamine receptor in the pathogenesis of genetic hypertension.

Since dopamine produced by the kidney is an intrarenal regulator of sodium transport, an abnormality of the dopaminergic system may be important in the pathogenesis of hypertension. In the spontaneously hypertensive rat (SHR), in spite of normal renal production of dopamine and receptor density, there is defective transduction of the D1 receptor signal in renal proximal tubules, resulting in decreased inhibition of sodium transport (Na+/H+ exchanger [NHE] and Na+/K+ATPase activity) by dopamine. To determine if impaired D1 receptor regulation of NHE in proximal tubules is related to hypertension, studies were performed in a F2 generation from female Wistar Kyoto (WKY) and male SHR crosses. A D1 agonist, SKF 81297, inhibited (37.6 +/- 4.7%) NHE activity in brush border membranes of normotensive F2s (systolic blood pressure < 140 mm Hg, n = 7) but not in hypertensive F2s (n = 21). Furthermore, a D1 agonist, SKF 38393, when infused into the renal artery, dose dependently increased sodium excretion in normotensive F2s (n = 3) without altering renal blood flow but was inactive in hypertensive F2s (n = 21). Since the major D1 receptor gene expressed in renal proximal tubules is the D1A subtype, we determined the importance of this gene in the control of blood pressure in mice lacking functional D1A receptors. Systolic blood pressure was greater in homozygous (n = 6) and heterozygous (n = 5) mice compared to normal sex matched litter mate controls (n = 12); moreover, the mice lacking one or both D1A alleles developed diastolic hypertension. The cosegregation with hypertension of an impaired D1 receptor regulation of renal sodium transport and the development of elevated systolic and diastolic pressure in mice lacking one or both D1A alleles suggest a causal relationship of the D1A receptor gene with hypertension.     

Cytoplasmic free [Ca2+] is not increased in the platelets of deoxycorticosterone-salt and spontaneously hypertensive rats

The cytoplasmic free calcium concentration ([Ca2+]i) in the platelets of spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), deoxycorticosterone-salt hypertensive rats (DOC) and normotensive Sprague-Dawley rats (SD) was measured with the fluorescent dye, quin-2-tetra-acetoxymethyl ester. No significant difference in platelet [Ca2+]i was found between SHR and WKY or between DOC and SD rats. No correlations were found between systolic blood pressure and [Ca2+]i. These results suggest that the elevation of platelet [Ca2+]i does not necessarily accompany hypertension in rats.     

Defective modulation of noradrenergic neurotransmission by endogenous prostaglandins in aging spontaneously hypertensive rats

Sympathetic nerve stimulation causes a greater vascular response in spontaneously hypertensive rats (SHR) compared to Wistar-Kyoto normotensive rats (WKY), i.e., noradrenergic neurotransmission is enhanced in SHR. Prejunctional and/or postjunctional defects in the regulation of noradrenergic neurotransmission by endogenous prostaglandins could contribute to the increased responsiveness to sympathetic nerve stimulation in SHR. This hypothesis was tested by comparing the effects in SHR vs. WKY of inhibition of cyclooxygenase on vascular responses to periarterial nerve stimulation (PNS), norepinephrine (NE) and angiotensin II (ang II) in the in situ blood perfused rat mesentery. The cyclooxygenase inhibitor, indomethacin, potentiated vascular responses to PNS and NE similarly in 16-week old SHR vs. age-matched WKY. However, in this age group, indomethacin enhanced responses to ang II more in SHR compared with WKY. To determine whether chronic exposure of the vasculature to high blood pressure might alter the physiological significance of prostaglandin-mediated regulation of noradrenergic neurotransmission in vivo, additional studies were conducted in SHR and WKY that were 25 weeks old. In this age group, neither indomethacin nor ibuprofen, an alternative cyclooxygenase inhibitor, significantly potentiated responses to either PNS or NE in SHR, whereas in WKY both indomethacin and ibuprofen potentiated responses to PNS and NE. Also, in these older animals, indomethacin and ibuprofen enhanced responses to ang II equally in SHR vs. WKY. These findings indicate that in aging SHR prostaglandin-mediated regulation of vascular responses to sympathetic nerve stimulation becomes defective. This defect may contribute to the worsening of high blood pressure with age and may be involved in some of the vascular pathology associated with hypertension.     

Glomerular injury in uninephrectomized spontaneously hypertensive rats. A consequence of glomerular capillary hypertension.

Micropuncture and/or morphologic studies were performed in intact Wistar-Kyoto rats (WKY) (group 0), intact spontaneously hypertensive rats (SHR) (groups 1 and 5), uninephrectomized (UNX) WKY (groups 2 and 6), and UNX SHR (groups 3 and 4, 7 and 8). UNX was performed when rats were 5 wk of age. Groups 0-4 were observed for 34 wk after which whole kidney clearance and morphologic studies were performed. Groups 5-8 underwent micropuncture study at 10 wk of age. Groups 4 and 8 were fed a diet containing 6% protein. All other rats ingested standard laboratory diet. 5 wk after UNX, normotensive group 6 had higher single nephron glomerular filtration rate (SNGFR) and initial glomerular plasma flow rate (QA) than intact, hypertensive group 5. Glomerular transcapillary hydraulic pressure difference (delta P) was similar in these two groups. Hypertensive group 7 exhibited less elevation in SNGFR and QA than group 6, but delta P was significantly increased. The presence of glomerular capillary hypertension in UNX SHR at 10 wk was associated with the development of significant proteinuria and an increased incidence of mesangial expansion and glomerular sclerosis at 7 mo (group 3) as compared with groups 0, 1, and 2. Protein restriction prevented the development of increased delta P in UNX SHR (group 8) and also conferred long-term protection from increased urinary protein excretion and glomerular injury (group 4). These studies suggest that glomerular capillary hypertension predisposes to glomerular injury in this model of hypertension with reduced renal mass.     

Age-dependent increase in arterial smooth muscle calcium in spontaneously hypertensive rats

Alterations in cellular calcium metabolism in essential hypertensive and in the SHR have been described. In the present study, particle-induced X-ray emission (PIXE) was used to get some information on the spatial distribution of Ca2+ in aortas of spontaneously hypertensive rats (SHR) and normotensive controls aged 1 week, 4 weeks, and 12 weeks. It was found that the Ca2+ content was not elevated in the aortic smooth muscle of SHR aged 1 week (n = 9) as compared to normotensive controls (n = 8) (186.8 +/- 89.9 micrograms Ca2+/g tissue vs 254.0 +/- 73.7 micrograms Ca2+/g tissue. The Ca2+ content was significantly raised in the aortic smooth muscle of SHR aged 4 weeks (n = 9) as compared to 4-weeks-old WKY rats (n = 12) (726.0 +/- 130.4 Ca2+/g tissue vs 440.3 +/- 214.4 Ca2+ micrograms/g tissue and in SHR aged 3 months (n = 15) as compared to WKY rats (n = 12), respectively (3317.0 +/- 734.0 micrograms Ca2+/g tissue vs. 1632.0 +/- 569.6 micrograms Ca2+/g tissue). The results confirm the age-related increase in the arterial Ca2+ content in normotensive rats and demonstrate additionally that this age-related rise in arterial Ca2+ content is accelerated in SHR.     

Smooth muscle alpha-2 adrenoceptors mediate vasoconstrictor responses to exogenous norepinephrine and to sympathetic stimulation to a greater extent in spontaneously hypertensive than in Wistar Kyoto rat tail arteries

The alpha adrenoceptor-mediated vasoconstriction in isolated perfused tail arteries from spontaneously hypertensive (SHR) and age matched Wistar Kyoto (WKY) normotensive rats has been examined. Responses induced by periarterial field stimulation, exogenous norepinephrine or the selective alpha-1 adrenoceptor agonist methoxamine were preferentially antagonized by prazosin in both SHR or WKY tail arteries. However, in SHR only, the alpha-2 adrenoceptor antagonist idazoxan (RX 781094) at low concentrations, significantly antagonized responses to periarterial field stimulation and to exogenous norepinephrine. Except at rather high concentrations, idazoxan was inactive as an antagonist of responses induced by methoxamine. The alpha-1 adrenoceptor blocking agent prazosin was a very potent antagonist of the responses induced by periarterial field stimulation and by methoxamine. These results indicate that alpha-2 adrenoceptors predominate in both SHR and WKY tail arteries, but a significant subpopulation of smooth muscle alpha-2 adrenoceptors is present in tail arteries of SHR but not of WKY rats. In contrast to WKY normotensive rats, postjunctional alpha-2 adrenoceptors may also be involved in the vasoconstrictor responses to sympathetic nerve stimulation in tail arteries of SHR.     

Cosegregation of the renin allele of the spontaneously hypertensive rat with an increase in blood pressure.

The spontaneously hypertensive rat (SHR) exhibits alterations in the renin-angiotensin-aldosterone system which are similar to those that characterize patients with "nonmodulating" hypertension, a common and highly heritable form of essential hypertension. Accordingly, we determined whether the inheritance of a DNA restriction fragment length polymorphism (RFLP) marking the renin gene of the SHR was associated with greater blood pressure than inheritance of a RFLP marking the renin gene of a normotensive control rat. In an F2 population derived from inbred SHR and inbred normotensive Lewis rats, we found the blood pressure in rats that inherited a single SHR renin allele to be significantly greater than that in rats that inherited only the Lewis renin allele. To the extent that the SHR provides a suitable model of "nonmodulating" hypertension, these findings raise the possibility that a structural alteration in the renin gene, or a closely linked gene, may be a pathogenetic determinant of increased blood pressure in one of the most common forms of essential hypertension in humans.     

Kappa opioid receptor activity in spontaneously hypertensive rats

Earlier studies from this laboratory had indicated that there is a selective increase in the density of brain kappa opioid receptors labeled with [3H]ethylketocyclazocine in spontaneously hypertensive (SHR) rats in comparison to normotensive Wistar-Kyoto rats. The binding of a mu-ligand, [3H]naltrexone, and a delta-ligand, [3H]Tyr-D-Ser-Gly-Phe-Leu-Thr, to brain membranes of hypertensive and normotensive rats did not differ. The present studies were undertaken to determine further the role of kappa opioid receptors in hypertension. The binding of [3H]ethylketocyclazocine to brain membranes of hypertensive rats was much greater than those of normotensive rats. The density of kappa receptors was significantly higher in hypothalamic membranes of hypertensive rats as compared to normotensive rats. In order to determine the functional significance of the increased density of brain kappa opioid receptors in SHR rats, the effect of the kappa receptor agonists, tifluadom, U-50,488H and bremazocine, on two known actions associated with kappa receptors, namely analgesia and diuresis, were determined in SHR and normotensive rats. All three kappa agonists produced dose-dependent analgesia as measured by the tail-flick test. The intensity of the analgesic responses at each dose of the drugs in SHR rats was much greater than in normotensive Wistar-Kyoto rats. The kappa drugs also produced dose-dependent diuretic effects when the rats were loaded with 5% saline intragastrically. The increases in the volumes of urine produced by kappa drugs were much greater in SHR rats in comparison to normotensive rats. The basal tail-flick reaction time or urinary output in the two strains did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exaggerated natriuresis in the conscious spontaneously hypertensive rat.

In response to an acute saline load, many patients with essential hypertension exhibit an exaggerated natriuresis relative to normotensive controls. In the present study, the urinary responses of conscious,Okamoto-strain, spontaneously hypertensive rats (SHR), and Wistar-Kyoto strain normotensive rats (NTR) to an acute saline load were evaluated to determine if a similar exaggerated natruiresis exists in this form of hypertension. Twelve rats of each strain per group (12 weeks of age) were housed in metabolism cages for 1 week. Systolic blood pressures (tail cuff) were significantly different (206+/- 9 mm. Hg in SHR and 135 +/- 3 mm. Hg in NTR). After a 4-hour control urine collection, 6 ml. of 0.9 per cent sodium chloride were given by gavage. Urine was collected again for 2 hours. Control urinary excretions of sodium, potassium, and creatinine in SHR and NTR were 11.2 +/- 4.8 muEq per hour, 50.1 +/- 7.6 muEq per hour, and 39.9 +/- 5.5 mg. per hour in SHR, and 13.8 +/- 2.4 muEq per hour, 34.9 +/- 5.5 muEq per hour, and 37.5 +/- 7.1 mg. per hour in NTR, respectively. The respective control values for sodium, potassium, and creatinine excretion in the two groups were not significantly different. Following the saline load, sodium and creatinine excretion rates were significantly elevated in both groups of rats. However, the increase in sodium excretion in SHR (60.8 +/- 7.2 MUEq per hour) was more than double and significantly different from that of the NTR (26.6 +/- 3.7 muEq per hour). In contrast, the increments in creatinine excretion in the two groups of rats were not significantly different from each other. In the NTS, urinary potassium excretion was significantly elevated (59.0 +/- 7.9 muEq per hour) whereas in SHR it was not significantly altered (12.0 +/- 8.8 muEq per hour). The change in urinary creatinine excretion as an index of change in glomerular filtration rate suggests that the greater increase in sodium excretion by the SHR was the result of decreased fractional reabsorption of sodium and not the result of a greater increase in glomerular filtration rate. The exaggerated natriuretic response to salt loading in SHR resembles that in hypertensive man except that in SHR, a simultaneous kaliuretic response is absent.     

Altered extracellular calcium homoeostasis in essential hypertension: a consequence of abnormal cell calcium handling

A number of abnormalities in the extracellular and intracellular handling of calcium in arterial hypertension, namely an increased urinary calcium excretion, a reduced serum ionized calcium level and an enhanced intracellular free calcium concentration, have previously been reported by this and other laboratories. The present study aimed to investigate the handling of an exogenous calcium load in hypertensive and normotensive subjects in order to detect possible differences with regard to tissue calcium metabolism in vivo. A constant rate intravenous calcium infusion (0.2 mmol 2 h-1 kg-1 body wt.) was carried out in the participants. Serum calcium concentrations were determined at regular intervals during the infusion and in the 4 h after the end of the calcium load. Over the same period, urinary calcium excretion was evaluated in timed urine collections. Hypertensive subjects had lower serum ionized calcium levels compared with normotensive subjects at all the experimental points, a finding suggestive of a faster disappearance of calcium from the circulation. The total body calcium clearance, calculated from the area under the curve of the serum calcium concentrations, was enhanced in hypertensive patients (P less than 0.03). Although the renal calcium excretion was higher in hypertension, the renal calcium clearance accounted for only a minor fraction of the total body clearance, suggesting that the reduced serum calcium levels achieved by the hypertensive patients were not explained by the renal calcium leak. The enhanced total body calcium clearance found in hypertensive subjects is therefore due to an increased tissue calcium uptake. This finding provides indirect evidence of an altered cell calcium handling in hypertension.     

Vasopressin-mediated contractions in mesenteric arteries from spontaneously hypertensive rats: differences in response compared with Wistar-Kyoto animals

1. The sensitivity of mesenteric resistance arterioles to [arginine]vasopressin (AVP) was investigated in spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY). No difference in pAVP (-log dose of AVP producing 50% of the maximum response) was observed [SHR 0.21 +/- 0.03 m-units/ml (n = 10) vs WKY 0.15 +/- 0.06 m-units/ml (n = 9)], although SHR vessels exhibited greater absolute tension development. 2. Both strains of rat displayed tachyphylaxis to repeated stimulation with AVP, and oscillatory tension changes were observed in all vessels from SHR and rarely in WKY vessels at activating concentrations of AVP. 3. AVP did not elicit a contractile response after noradrenaline-induced calcium depletion. 4. After vessels were depleted of calcium by using a combination of calcium-free media and noradrenaline stimulation, restoration of calcium in the presence of AVP elicited a greater contractile response in SHR vessels. 5. The results therefore provide evidence for an increased calcium response to AVP in SHR resistance vessels, although this was only demonstrable by calcium recovery experiments.